microRNA-499a promotes the progression and chemoresistance of cervical cancer cells by targeting SOX6
AbstractEmerging evidence has indicated that microRNAs are involved in multiple processes of cancer development. Previous studies have demonstrated that microRNA-499a (miR-499a) plays both oncogenic and tumor suppressive roles in several types of malignancies, and genetic variants in miR-499a are associated with the risk of cervical cancer. However, the biological roles of miR-499a in cervical cancer have not been investigated. Quantitative real-time PCR was used to assess miR-499a expression in cervical cancer cells. Mimics or inhibitor of miR-499a was transfected into cervical cancer cells to upregulate or downregulate m...
Source: Apoptosis - January 14, 2020 Category: Molecular Biology Source Type: research
Necroptosis and its role in infectious diseases
AbstractNecroptosis is a noncaspase-dependent and precisely regulated mechanism of cell death. Necroptosis is mainly initiated by members of the tumor necrosis factor receptor (TNFR) and Toll-like receptor (TLR) families, interferon, intracellular RNA and DNA sensors and other mediators. Subsequently, the protein kinase RIPK1 (receptor-interacting protein kinase 1) and RIPK3 interact with the receptor protein, which transduces death signals and further recruits and phosphorylates MLKL (mixed lineage kinase domain-like protein). MLKL serves as the initiator of cell death and eventually induces necroptosis. It was found that...
Source: Apoptosis - January 7, 2020 Category: Molecular Biology Source Type: research
PDGFR β-targeted TRAIL specifically induces apoptosis of activated hepatic stellate cells and ameliorates liver fibrosis
In this study, we found that platelet-derived growth factor receptor β (PDGFRβ) was co-expressed with DR5 in aHSCs. And the ZPDGFR β affibody with high affinity for PDGFR β could bind aHSCs and, thus, accumulate in the fibrotic liver. ZPDGFR β was fused to hTRAIL to produce the fusion protein Z-hTRAIL. Compared to hTRAIL, Z-hTRAIL showed greater in vitro cell binding and apoptosis-induction in aHSCs. In addition, Z-hTRAIL induced apoptosis of aHSCs but spared other normal liver cells. In vivo, Z-hTRAIL accumulated preferentially in fibrotic livers and exerted greater effects than hTRAIL in inducing...
Source: Apoptosis - January 1, 2020 Category: Molecular Biology Source Type: research
Artemisinin and dihydroartemisinin promote β-cell apoptosis induced by palmitate via enhancing ER stress
In this study, the rat pancreatic β-cell line INS-1 and mouse pancreatic β-cell line MIN6 were cultured with palmitate (PA) (0.1 mM) to induce cell apoptosis in the presence or absence of ART or DHA. Cell apoptosis was investigated by using flow cytometry, and the expression of ER stress markers, including CHOP, GRP78 and PDI, was detected by Western blotting and/or qRT-PCR. The results showed that ART and DHA significantly increased the apoptosis of β-cells induced by PA and exacerbated the ER stress caused by PA. An inhibitor of ER stress, 4-phenylbutyric acid (4-PBA), sig nificantly ameliorated cell ...
Source: Apoptosis - January 1, 2020 Category: Molecular Biology Source Type: research
Lysophosphatidic acid promotes survival of T lymphoma cells by altering apoptosis and glucose metabolism
AbstractLysophosphatidic acid (LPA) is a bioactive lipid, which plays an indispensable role in various physiological and pathological processes. Moreover, an elevated level of LPA has been observed in malignancies of different origins and implicated in their progression via modulation of proliferation, apoptosis, invasion and metastasis. Interestingly, few recent reports suggest a pivotal role of LPA-modulated metabolism in oncogenesis of ovarian cancer. However, little is understood regarding the role of LPA in the development and progression of T cell malignancies, which are considered as one of the most challenging neop...
Source: Apoptosis - December 23, 2019 Category: Molecular Biology Source Type: research
Liposomal encapsulation of silver nanoparticles (AgNP) improved nanoparticle uptake and induced redox imbalance to activate caspase-dependent apoptosis
AbstractMacrophages play a crucial role in several diseases ’ development and progression, such as in cancer and arthritis through ROS generation and inflammation. This makes macrophages a therapeutic target in these diseases. While silver nanoparticles (AgNP) have been widely used as an antibacterial and investigated as anticancer, its potential against m acrophages may be limited due to its inherent oxidative mechanism. Here we encapsulated AgNP in a dipalmitoyl-phosphatidyl choline (DPPC) liposome (forming Lipo-AgNP) to suppress AgNP-induced ROS and enhance its cytotoxicity against THP1-differentiated macrophages ...
Source: Apoptosis - December 20, 2019 Category: Molecular Biology Source Type: research
MicroRNA-214 targets COX-2 to antagonize indoxyl sulfate (IS)-induced endothelial cell apoptosis
In conclusion, this study demonstrated an important role of miR-214 in protecting against endothelial cell damage induced by IS possibly by direct downregulation of COX-2/PGE2 axis. (Source: Apoptosis)
Source: Apoptosis - December 9, 2019 Category: Molecular Biology Source Type: research
Correction to: M1 macrophage dependent-p53 regulates the intracellular survival of mycobacteria
The original version of this article unfortunately contains an error in the acknowledgement section. The text “Brain Korea 21 PLUS Project for Medical Science, Chungnam National University” was omitted by mistake. The correct and complete acknowledgment is given below: Acknowledgments This work was supported by the research fund of Chungnam National University and the Brain Korea 21 PLUS Project for Med ical Science, Chungnam National University. The funders had no role in study design, data collection and analysis decision to publish, or preparation of the manuscript. (Source: Apoptosis)
Source: Apoptosis - November 27, 2019 Category: Molecular Biology Source Type: research
Effect of miR-27b-5p on apoptosis of human vascular endothelial cells induced by simulated microgravity
AbstractWeightlessness-induced cardiovascular dysfunction can lead to physiological and pathological consequences. It has been shown that spaceflight or simulated microgravity can alter expression profiles of some microRNAs (miRNAs). Here, we attempt to identify the role of miRNAs in human umbilical vein endothelial cells (HUVECs) apoptosis under simulated microgravity. RNA-sequencing and quantitative real-time PCR (qRT-PCR) assays were used to identify differentially expressed miRNAs in HUVECs under simulated microgravity. Then we obtained the target genes of these miRNAs through target analysis software. Moreover, GO and...
Source: Apoptosis - November 25, 2019 Category: Molecular Biology Source Type: research
Klotho-mediated changes in the expression of Atg13 alter formation of ULK1 complex and thus initiation of ER- and Golgi-stress response mediated autophagy
In this study, we have performed a detailed step-by-step analysis of autophagy flux-related genes ’ expression and endoplasmic reticulum and Golgi stress related pathways in order to determine the exact mechanistic event when autophagy is inhibited in klotho-deficient cells on account of apoptosis initiation. We provide evidence thatklotho-silencing in LPS-treated cells results in differential course of ER- and Golgi-mediated stress response. Further, we show that inklotho-deficient cells formation of ULK1 complex is inhibited and thus autophagy initiation is blocked on the account of apoptosis activation, while in t...
Source: Apoptosis - November 15, 2019 Category: Molecular Biology Source Type: research
M1 macrophage dependent-p53 regulates the intracellular survival of mycobacteria
In this study, we found that the p53-deficient macrophages failed to controlMycobacterium tuberculosis (Mtb), manifested as a lower apoptotic cell death rate and enhanced intracellular survival. The expression levels of p53 during Mtb infection were stronger in M1 macrophages than in M2 macrophages. The TLR2/JNK signaling pathway plays an essential role in the modulation of M1 macrophage polarization upon Mtb infection. It facilitates p53-mediated apoptosis through the production of reactive oxygen species, nitric oxide and inflammatory cytokines in Mtb-infected M1 macrophages. In addition, nutlin-3 effectively abrogated t...
Source: Apoptosis - November 5, 2019 Category: Molecular Biology Source Type: research
Influenza A virus-induced apoptosis and virus propagation
AbstractInfluenza A viruses (IAVs) are respiratory pathogens that cause severe morbidity and mortality worldwide. They affect cellular processes such as proliferation, protein synthesis, autophagy, and apoptosis. Although apoptosis is considered an innate cellular response to invading infectious pathogens, IAVs have evolved to encode viral proteins that modulate host cellular apoptosis in ways that support efficient viral replication and propagation. An understanding of the modulation of host responses is essential to the development of novel therapeutics for the treatment of IAV infections. In this review, we discuss the ...
Source: Apoptosis - October 30, 2019 Category: Molecular Biology Source Type: research
Inhibitors of HSP90 in melanoma
AbstractHSP90 (heat shock protein 90) is an ATP-dependent molecular chaperone involved in a proper folding and maturation of hundreds of proteins. HSP90 is abundantly expressed in cancer, including melanoma. HSP90 client proteins are the key oncoproteins of several signaling pathways controlling melanoma development, progression and response to therapy. A number of natural and synthetic compounds of different chemical structures and binding sites within HSP90 have been identified as selective HSP90 inhibitors. The majority of HSP90-targeting agents affect N-terminal ATPase activity of HSP90. In contrast to N-terminal inhib...
Source: Apoptosis - October 28, 2019 Category: Molecular Biology Source Type: research
Accumulation of tissue factor in endothelial cells promotes cellular apoptosis through over-activation of Src1 and involves β1-integrin signalling
In this study, the involvement of Src1 in the induction of TF-mediated cell apoptosis, and the mechanisms of Src1 activation were investigated. Human coronary artery endothelial cell (HCAEC) were transfected with plasmids to express the wild-type TF (TFWt-tGFP), or a mutant (Ser253 → Ala) which is incapable of being released from cells (TFAla253-tGFP). The cells were then activated with PAR2-agonist peptide (SLIGKV-NH) and the phosphorylation of Src and Rac, and also the kinase activity of Src were assessed. Transfected cells were also pre-incubated with pp60c Src inhibitor, FAK inhibitor-14, or a block...
Source: Apoptosis - October 25, 2019 Category: Molecular Biology Source Type: research
Integrin-EGFR interaction regulates anoikis resistance in colon cancer cells
AbstractAnoikis resistance is an essential property of cancer cells that allow the extra-cellular matrix-detached cells to survive in a suspended state in body fluid in order to metastasize and invade to distant organs. It is known that integrins play an important role in anoikis resistance, but detailed mechanisms are not well understood. Here we report that highly metastatic colon cancer cells showed a higher degree of anoikis resistance than the normal intestinal epithelial cells. These anoikis-resistant cancer cells express high-levels of integrin- α2, β1, and activated EGFR in the anchorage-independent stat...
Source: Apoptosis - October 22, 2019 Category: Molecular Biology Source Type: research
Two-factor specification of apoptosis: TGF- β signaling acts cooperatively with ecdysone signaling to induce cell- and stage-specific apoptosis of larval neurons during metamorphosis in Drosophila melanogaster
AbstractDevelopmentally regulated programmed cell death (PCD) is one of the key cellular events for precise controlling of neuronal population during postembryonic development of the central nervous system. Previously we have shown that a group of corazonin-producing peptidergic neurons (vCrz) undergo apoptosis in response to ecdysone signaling via ecdysone receptor (EcR)-B isoforms and Ultraspiracle during early phase of metamorphosis. Further utilizing genetic, transgenic, and mosaic analyses, we have found that TGF- β signaling mediated by a glia-produced ligand, Myoglianin, type-I receptor Baboon (particularly Bab...
Source: Apoptosis - October 22, 2019 Category: Molecular Biology Source Type: research
PP2Ac upregulates PI3K-Akt signaling and induces hepatocyte apoptosis in liver donor after brain death
AbstractMultiple research groups have demonstrated that the outcome of patients receiving liver grafts from brain death donors (DBD) is poorer when compared with patients receiving grafts from living donors. This might be due to an increased hepatocyte apoptosis induced after brain death (BD). In this work, we found that the activity of PP2A-Akt pathway is significantly increased in clinical donor ex vivo hepatocytes after BD by iTRAQ protein quantification analysis. The same results were confirmed in animal models. A time-dependent promotion of apoptosis was also found in DBD rabbit liver, as demonstrated by the increased...
Source: Apoptosis - October 11, 2019 Category: Molecular Biology Source Type: research
Loss of HMBOX1 promotes LPS-induced apoptosis and inhibits LPS-induced autophagy of vascular endothelial cells in mouse
In conclusion, HMBOX1 participated in the functional maintenance of mouse aortic endothelial cells, the aortic endothelial cells of HMBOX1 KO mouse showed increased apopt osis and decreased autophagy with LPS treatment. (Source: Apoptosis)
Source: Apoptosis - October 3, 2019 Category: Molecular Biology Source Type: research
Liver-specific Bid silencing inhibits APAP-induced cell death in mice
In conclusion, the liver-specific silencing of Bid expression did not protect APAP-exposed mice from microcirculatory dysfunction, but markedly protected the liver from necrotic cell death and in consequence from sterile inflammation. The study contributes to the understanding of the molecular mechanism of the APAP-induced pathogenic pathway by strengthening the importance of Bid and Bid silencing associated effects. (Source: Apoptosis)
Source: Apoptosis - October 1, 2019 Category: Molecular Biology Source Type: research
Correction to: Defining the role of cytoskeletal components in the formation of apoptopodia and apoptotic bodies during apoptosis
The original version of the article unfortunately contained a typo in the fourth author name. The author name was incorrectly listed as Rochelle Tixeria. The correct name should be Rochelle Tixeira. The original article has been corrected. (Source: Apoptosis)
Source: Apoptosis - September 23, 2019 Category: Molecular Biology Source Type: research
Oroxylin A induces apoptosis of activated hepatic stellate cells through endoplasmic reticulum stress
In conclusion, our findings suggest a role for ERS in the mechanism underlying amelioration of hepatic fibrosis by OA. (Source: Apoptosis)
Source: Apoptosis - September 20, 2019 Category: Molecular Biology Source Type: research
Defining the role of cytoskeletal components in the formation of apoptopodia and apoptotic bodies during apoptosis
AbstractDuring apoptosis, dying cells undergo dynamic morphological changes that ultimately lead to their disassembly into fragments called apoptotic bodies (ApoBDs). Reorganisation of the cytoskeletal structures is key in driving various apoptotic morphologies, including the loss of cell adhesion and membrane bleb formation. However, whether cytoskeletal components are also involved in morphological changes that occur later during apoptosis, such as the recently described generation of thin apoptotic membrane protrusions called apoptopodia and subsequent ApoBD formation, is not well defined. Through monitoring the progres...
Source: Apoptosis - September 5, 2019 Category: Molecular Biology Source Type: research
Rotenone protects against β-cell apoptosis and attenuates type 1 diabetes mellitus
AbstractType 1 diabetes mellitus (T1DM) is caused by pancreatic β-cell dysfunction and apoptosis, with consequent severe insulin deficiency. Thus, β-cell protection may be a primary target in the treatment of T1DM. Evidence has demonstrated that defective mitochondrial function plays an important role in pancreatic β-cell dysfunction and apoptosis; however, t he fundamental effect of mitochondrial complex I action on β-cells and T1DM remains unclear. In the current study, the pancreas protective effect of complex I inhibitor rotenone (ROT) and its potential mechanism were assessed in a streptozotocin (S...
Source: Apoptosis - September 4, 2019 Category: Molecular Biology Source Type: research
Combination of ERK2 inhibitor VX-11e and voreloxin synergistically enhances anti-proliferative and pro-apoptotic effects in leukemia cells
In conclusion, combination of VX-11e and voreloxin can exert a synergistic anticancer effect in leukemia cells. (Source: Apoptosis)
Source: Apoptosis - September 3, 2019 Category: Molecular Biology Source Type: research
TNF- α-elicited miR-29b potentiates resistance to apoptosis in peripheral blood monocytes from patients with rheumatoid arthritis
AbstractCD14-positive monocytes from patients with rheumatoid arthritis (RA) are more resistant to apoptosis, which promotes their persistence at the inflammatory site and thereby contributes crucially to immunopathology. We sought to elucidate one mechanism underlying this unique pathogenesis: resistance to apoptosis and the potential involvement of miR-29b in this process. CD14-positive peripheral blood monocytes (PBMs) from RA patients were observed to be resistant to spontaneous apoptosis compared to PBMs from healthy volunteers. Intriguingly, expression of miR-29b was significantly upregulated in PBMs from RA patients...
Source: Apoptosis - August 31, 2019 Category: Molecular Biology Source Type: research
Correction to: SPECT/CT imaging of apoptosis in aortic aneurysm with radiolabeled duramycin
The original version of this article unfortunately contains errors in Figure 4. An incorrect Figure 4D is published which is actually a repetition of Figure 2C (i.e., apoptosis rate in control vs. H2O2-treated group). The correct Figure 4D should be the aortic diameter of control vs. experimental groups. Also, the order of part figures (a\b\c\d) in Figure 4E is incorrect. The correct Figure 4 is given below. (Source: Apoptosis)
Source: Apoptosis - August 17, 2019 Category: Molecular Biology Source Type: research
Autophagy protects HUVECs against ER stress-mediated apoptosis under simulated microgravity
AbstractAstronauts exposed to a gravity-free environment experience cardiovascular deconditioning that causes post-spaceflight orthostatic intolerance and other pathological conditions. Endothelial dysfunction is an important factor responsible for this alteration. Our previous study showed enhanced autophagy in endothelial cells under simulated microgravity. The present study explored the cytoprotective role of autophagy under microgravity in human umbilical vein endothelial cells (HUVECs). We found that clinorotation for 48 h induced apoptosis and endoplasmic reticulum (ER) stress in HUVECs. ER stress and the ...
Source: Apoptosis - July 29, 2019 Category: Molecular Biology Source Type: research
MAGI1 mediates tumor metastasis through c-Myb/miR-520h/MAGI1 signaling pathway in renal cell carcinoma
In this study, we demonstrated that MAGI1 was markedly decreased in the RCC and indicated poor survival. Furthermore, we found that MAGI1 suppressed the invasion and migration of human RCC cells. Mechanistic investigations revealed that MAGI1 stabilized the PTEN/MAGI1/ β-catenin complex to inhibit β-catenin signaling pathway. Moreover, MAGI1 was targeted by miR-520h which was transcriptionally activated by c-Myb. Collectively, our findings suggested that MAGI1mediated tumor metastasis through c-Myb/miR-520h/MAGI1 signaling pathway in RCC. (Source: Apoptosis)
Source: Apoptosis - July 27, 2019 Category: Molecular Biology Source Type: research
Deubiquitylatinase inhibitor b-AP15 induces c-Myc-Noxa-mediated apoptosis in esophageal squamous cell carcinoma
AbstractEsophageal squamous cell carcinoma (ESCC) is one of the most malignant tumors in east Asia. However, the molecular mechanism underlying its progression remains unclear. The ubiquitin –proteasome system (UPS) is a central mechanism for protein degradation and turnover. Accumulating evidence showed that more and more deubiquitinases could serve as attractive anti-cancer target. The expression of USP14 and UCH37 in esophagus squamous cell carcinoma tissues were examined by immuno histochemistry and western blot assays. Effect of b-AP15, a USP14 and UCH37 inhibitor, on ESCC cell growth was evaluated by cell viabi...
Source: Apoptosis - July 24, 2019 Category: Molecular Biology Source Type: research
Inhibition of SIRT1/2 upregulates HSPA5 acetylation and induces pro-survival autophagy via ATF4-DDIT4-mTORC1 axis in human lung cancer cells
AbstractSirtuins have emerged as a promising novel class of anti-cancer drug targets. Inhibition of SIRT1 and SIRT2 induces apoptosis in cancer cells and they play multifaceted roles in regulating autophagy. In the present study, we found that salermide, a SIRT1/2-specific inhibitor or small interfering RNAs (siRNAs) to block SIRT1/2 expression could induce autophagy in human NSCLC cells. Moreover, SIRT1/2 inhibition increased the expression levels of ATF4 and DDIT4 and downregulated p-RPS6KB1 and p-EIF4EBP1, two downstream molecules of mTORC1. Moreover, ATF4 or DDIT4 knockdown attenuated salermide-induced autophagy, sugge...
Source: Apoptosis - July 18, 2019 Category: Molecular Biology Source Type: research
Hyperosmotic stress promotes endoplasmic reticulum stress-dependent apoptosis in adult rat cardiac myocytes
AbstractIn different pathological situations, cardiac cells undergo hyperosmotic stress and cell shrinkage. This change in cellular volume has been associated with contractile dysfunction and cell death. However, the intracellular mechanisms involved in hyperosmotic stress-induced cell death have not been investigated in depth in adult cardiac myocytes. Given that osmotic stress has been shown to promote endoplasmic reticulum stress (ERS), a recognized trigger for apoptosis, we examined whether hyperosmotic stress triggers ERS in adult cardiac myocytes and if so whether this mechanism mediates hyperosmotic stress-induced c...
Source: Apoptosis - July 15, 2019 Category: Molecular Biology Source Type: research
Neuronal life or death linked to depression treatment: the interplay between drugs and their stress-related outcomes relate to single or combined drug therapies
In conclusion, our findings may pave the way to better understanding of the stress-related effects on neurons associated with mono- and combined therapy with antidepressants. (Source: Apoptosis)
Source: Apoptosis - July 5, 2019 Category: Molecular Biology Source Type: research
Apoptosis regulation in the penumbra after ischemic stroke: expression of pro- and antiapoptotic proteins
AbstractIschemic stroke is the leading cause of human disability and mortality in the world. The main problem in stroke therapy is the search of efficient neuroprotector capable to rescue neurons in the potentially salvageable transition zone (penumbra), which is expanding after brain damage. The data on molecular mechanisms of penumbra formation and expression of diverse signaling proteins in the penumbra during first 24 h after ischemic stroke are discussed. Two basic features of cell death regulation in the ischemic penumbra were observed: (1) both apoptotic and anti-apoptotic proteins are simultaneously over-expr...
Source: Apoptosis - June 29, 2019 Category: Molecular Biology Source Type: research
JNK inhibition blocks piperlongumine-induced cell death and transcriptional activation of heme oxygenase-1 in pancreatic cancer cells
AbstractPiperlongumine (PL) is an alkaloid that inhibits glutathioneS-transferase pi 1 (GSTP1) activity, resulting in elevated reactive oxygen species (ROS) levels and cancer-selective cell death. We aimed to identify stress-associated molecular responses to PL treatment in pancreatic ductal adenocarcinoma (PDAC) cells. GSTP1 directly interacts with JNK, which is activated by oxidative stress and can lead to decreased cancer cell proliferation and cell death. Therefore, we hypothesized that JNK pathways are activated in response to PL treatment. Our results show PL causes dissociation of GSTP1 from JNK; robust JNK, c-Jun, ...
Source: Apoptosis - June 26, 2019 Category: Molecular Biology Source Type: research
Aspirin induces oncosis in tumor cells
AbstractIn contrast to the well-known anti-tumor mechanisms of aspirin in inducing apoptosis or autophagy, we here for the first time report oncosis induced by aspirin in tumor cells. In vitro and in vivo analysis showed that aspirin induced compromised Bcl-XL level and subsequent ATP depletion. Overexpression of CFP-Bcl-XL in Hela and A549 cells observably inhibited aspirin-induced ATP depletion and almost completely inhibited the aspirin-induced cells bubbling, while pharmacological inhibition of endogenous Bcl-XL activity by ABT-737 remarkably promoted aspirin-induced ATP depletion and cells bubbling, suggesting the key...
Source: Apoptosis - June 26, 2019 Category: Molecular Biology Source Type: research
Fipronil induces apoptosis and cell cycle arrest in porcine oocytes during in vitro maturation
In conclusion, FPN induces apoptosis and cell cycle arrest in porcine oocyte maturation because of increased ROS levels and DNA damage. This suggests that the FPN in the environment may have potential detrimental effects on the female mammalian reproductive system. (Source: Apoptosis)
Source: Apoptosis - June 25, 2019 Category: Molecular Biology Source Type: research
SPECT/CT imaging of apoptosis in aortic aneurysm with radiolabeled duramycin
The objective of this research was to estimate whether a[99mTc]duramycin probe can be used for apoptosis imaging in patients with aortic aneurysm (AA). Vascular smooth muscle cell (SMC) apoptosis has an important influence on AA development. Thus, non-invasive imaging of SMC apoptosis may be able to evaluate AA progress and risk stratification. SMCs were treated with hydrogen peroxide (H2O2; 200 μΜ) or culture medium as a control. Apoptosis was measured using flow cytometry and[99mTc]duramycin to detect the binding efficiency to apoptotic SMCs. C57/BL6 mice were administered angiotensin-II and beta-aminopropion...
Source: Apoptosis - June 21, 2019 Category: Molecular Biology Source Type: research
CNOT3 contributes to cisplatin resistance in lung cancer through inhibiting RIPK3 expression
In this study, after screening theCNOT3 mRNA in a cancer microarray database called Oncomine and examining the expression levels ofCNOT3 mRNA in normal tissues and lung cancer tissues, we found thatCNOT3 was up-regulated in lung cancer tissues. Besides, its high-expression was associated with poor prognosis of lung cancer patients. We also found higher expression level of CNOT3 and lower expression level of receptor-interacting protein kinase 3 (RIPK3) in cisplatin-resistant A549 (A549/DDP) cells, and knocking down CNOT3 expression could sensitize A549/DDP cells to cisplatin-induced apoptosis. We demonstrated that CNOT3 de...
Source: Apoptosis - June 8, 2019 Category: Molecular Biology Source Type: research
ATP induces caspase-3/gasdermin E-mediated pyroptosis in NLRP3 pathway-blocked murine macrophages
In this study, we used cellular models to mimic such blockade of NLRP3 activation: bone marrow-derived macrophages (BMDMs) treated with NLRP3-specific inhibitor MCC950 and RAW264.7 cells deficient in ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) expression. The results showed that ATP treatment induced lytic cell death morphologically resembling canonical pyroptosis in both MCC950-treated BMDMs and RAW264.7 cells, but did not cause the activation of caspase-1 (by detecting caspase-1p10 and mature interleukin-1 β) and cleavage of GSDMD. Instead, both apoptotic initiator (caspase-...
Source: Apoptosis - June 7, 2019 Category: Molecular Biology Source Type: research
MicroRNA-3607 inhibits the tumorigenesis of colorectal cancer by targeting DDI2 and regulating the DNA damage repair pathway
In this study, we analyzed miR-3607 expression Pan-Cancer data from the NCI ’s Genomic Data Commons (GDC) and found that miR-3607 was downregulated in lymphatic invasion patients and in recurrent cancer and correlated with Pan-Cancer patient survival. Functional studies indicated that the overexpression of miR-3607 decreased CRC cell proliferation, migration and invasion. Additionally, we used gene set enrichment analysis (GSEA), Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and a protein–protein interaction network to demonstrate that miR-3607 affects the DDR...
Source: Apoptosis - May 27, 2019 Category: Molecular Biology Source Type: research
Berberine mitigates IL-21/IL-21R mediated autophagic influx in fibroblast-like synoviocytes and regulates Th17/Treg imbalance in rheumatoid arthritis
AbstractIn our previous study, we explored the therapeutic effect of berberine (BBR) against IL-21/IL-21R mediated inflammatory proliferation of adjuvant-induced arthritic fibroblast-like synoviocytes (AA-FLS) through the PI3K/Akt pathway. The current study was designed to explore the therapeutic potential of BBR (15 –45 µM) against IL-21/IL-21R mediated autophagy in AA-FLS mediated through PI3K/Akt signaling and Th17/Treg imbalance. Upon IL-21 stimulation, AA-FLS expressed elevated levels of autophagy-related 5 (Atg5), Beclin-1 and LC3-phosphatidylethanolamine conjugate 3-II (LC3-II) through the utilizati...
Source: Apoptosis - May 20, 2019 Category: Molecular Biology Source Type: research
Letter to the editor regarding article, “Role of glycogen synthase kinase following myocardial infarction and ischemia–reperfusion”
Source: Apoptosis - May 11, 2019 Category: Molecular Biology Source Type: research
Endothelin-1-mediated cerebral ischemia in mice: early cellular events and the role of caspase-3
AbstractOver the past 30 years a number of animal models of cerebral ischemic injury have been developed. Middle cerebral artery occlusion (MCAO) in particular reproduces both ischemic and reperfusion elements and is widely utilized as a model of ischemic stroke in rodents. However substantial variability exists in this m odel even in clonal inbred mice due to stochastic elements of the cerebral vasculature. Models such as MCAO thus exhibit significant irreducible variabilities with respect to their zone of injury as well as inducing a sizable volume of injury to the cerebrum with damage to sub-cortical structures, c...
Source: Apoptosis - May 9, 2019 Category: Molecular Biology Source Type: research
Copper-imidazo[1,2- a ]pyridines induce intrinsic apoptosis and modulate the expression of mutated p53, haem-oxygenase-1 and apoptotic inhibitory proteins in HT-29 colorectal cancer cells
In conclusion, the copper-imidazo[1,2-a]pyridines were effective inducers of apoptotic cell death at low micromolar concentrations and changed the expression levels of proteins important for cell survival and cell death. These copper complexes may be useful tools to better understand the complexity of signalling networks in cancer cell death in response to cell stress. (Source: Apoptosis)
Source: Apoptosis - May 9, 2019 Category: Molecular Biology Source Type: research
Modulation of CD95-mediated signaling by post-translational modifications: towards understanding CD95 signaling networks
AbstractCD95 is a member of the death receptor family and is well-known to promote apoptosis. However, accumulating evidence indicates that in some context CD95 has not only the potential to induce apoptosis but also can trigger non-apoptotic signal leading to cell survival, proliferation, cancer growth and metastasis. Despite extensive investigations focused on alterations in the expression level of CD95 and associated signal molecules, very few studies, however, have investigated the effects of post-translational modifications such as glycosylation, phosphorylation, palmitoylation, nitrosylation and glutathionylation on ...
Source: Apoptosis - May 8, 2019 Category: Molecular Biology Source Type: research
Role of glycogen synthase kinase following myocardial infarction and ischemia –reperfusion
Source: Apoptosis - April 27, 2019 Category: Molecular Biology Source Type: research
Cellular responses of BRCA1 -defective HCC1937 breast cancer cells induced by the antimetastasis ruthenium(II) arene compound RAPTA-T
In this study, the effects of RAPTA-T onBRCA1-defective HCC1937 breast cancer cells have been investigated, and compared to its effects onBRCA1-competent MCF-7 breast cancer cells. RAPTA-T showed a very low cytotoxicity against both tested cells. Ruthenium is found mostly in the cytoplasmic compartment of both cells. Flow cytometric analysis reveals that the compound arrests the growth of both cells by triggering the G2/M phase that led to the induction of apoptosis. At equimolar concentrations, RAPTA-T causes much more cellularBRCA1 damage in HCC1937 than in MCF-7 cells, suppressing the expression ofBRCA1 mRNA in both cel...
Source: Apoptosis - April 23, 2019 Category: Molecular Biology Source Type: research
Proteasome inhibitors trigger mutations via activation of caspases and CAD, but mutagenesis provoked by the HDAC inhibitors vorinostat and romidepsin is caspase/CAD-independent
AbstractGenotoxic anti-cancer therapies such as chemotherapy and radiotherapy can contribute to an increase in second malignancies in cancer survivors due to their oncogenic effects on non-cancerous cells. Inhibition of histone deacetylase (HDAC) proteins or the proteasome differ from chemotherapy in that they eliminate cancer cells by regulating gene expression or cellular protein equilibrium, respectively. As members of these drug classes have been approved for clinical use in recent times, we investigated whether these two drug classes exhibit similar mutagenic capabilities as chemotherapy. The HDAC inhibitors vorinosta...
Source: Apoptosis - April 17, 2019 Category: Molecular Biology Source Type: research
17-Aminogeldanamycin selectively diminishes IRE1 α-XBP1s pathway activity and cooperatively induces apoptosis with MEK1/2 and BRAF V600E inhibitors in melanoma cells of different genetic subtypes
AbstractOutcomes of melanoma patient treatment remain unsatisfactory despite accessibility of oncoprotein-targeting drugs and immunotherapy. Here, we reported that 17-aminogeldanamycin more potently activated caspase-3/7 in BRAFV600E melanoma cells than geldanamycin, another inhibitor of heat shock protein 90 (HSP90). 17-aminogeldanamycin alleviated self-triggered compensatory increase in HSP70 mRNA level and induced endoplasmic reticulum (ER) stress, which was followed by selective diminution of cytoprotective IRE1 α-XBP1s pathway activity of unfolded protein response (UPR), inhibition of ERK1/2 activity and inducti...
Source: Apoptosis - April 15, 2019 Category: Molecular Biology Source Type: research
Matrix metalloproteinase 9 induces keratinocyte apoptosis through FasL/Fas pathway in diabetic wound
This study increases understanding of elevated MMP9 which is involved in diabetic wound repair and offers some insights into novel future therapies. (Source: Apoptosis)
Source: Apoptosis - April 4, 2019 Category: Molecular Biology Source Type: research