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Condition: Mitochondrial Disease

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Total 454 results found since Jan 2013.

Novel Roles of Mitochondrial Uniporter in Ovarian Cancer Cell Biology
This study highlights the potential of nanomaterials as a tool to broaden our understanding of cellular processes, establishes MICU1 as a novel regulator of the machinery in cancer cells that prevents apoptosis, and emphasizes the need to synergize nanoparticle design with understanding of mitochondrial machinery for enhancing targeted cellular toxicity.
Source: Journal of Biological Chemistry - June 14, 2013 Category: Chemistry Authors: Arvizo, R. R., Moyano, D. F., Saha, S., Thompson, M. A., Bhattacharya, R., Rotello, V. M., Prakash, Y. S., Mukherjee, P. Tags: Signal Transduction Source Type: research

TR3 Dysfunction in Ovarian Cancer
In metastatic ovarian cancer, resistance to platinum chemotherapy is common. Although the orphan nuclear receptor TR3 (nur77/NR4A1) is implicated in mediating chemotherapy-induced apoptosis in cancer cells, its role in ovarian cancer has not been determined. In an ovarian cancer tissue microarray, TR3 protein expression was elevated in stage I tumors, but downregulated in a significant subset of metastatic tumors. Moreover, TR3 expression was significantly lower in platinum-resistant tumors in patients with metastatic disease, and low TR3 staining was associated with poorer overall and progression-free survival. We have id...
Source: Cancer Research - July 31, 2013 Category: Cancer & Oncology Authors: Wilson, A. J., Liu, A. Y., Roland, J., Adebayo, O. B., Fletcher, S. A., Slaughter, J. C., Saskowski, J., Crispens, M. A., Jones, H. W., James, S., Fadare, O., Khabele, D. Tags: Molecular and Cellular Pathobiology Source Type: research

Nox2 as a potential target of mitochondrial superoxide and its role in endothelial oxidative stress.
Abstract Superoxide (O2•) production by the NADPH oxidases is implicated in the pathogenesis of many cardiovascular diseases, including hypertension. We have previously shown that activation of NADPH oxidases increases mitochondrial O2• which is inhibited by the ATP-sensitive potassium channel (mitoK+ATP) inhibitor, 5-hydroxydecanoic acid, and that scavenging of mitochondrial or cytoplasmic O2• inhibits hypertension. We hypothesized that mitoK+ATP-mediated mitochondrial O2• potentiates cytoplasmic O2• by stimulation of NADPH oxidases. In this work we studied Nox isoforms as a potential target of mitochon...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 16, 2013 Category: Physiology Authors: Nazarewicz RR, Dikalova AE, Bikineyeva A, Dikalov SI Tags: Am J Physiol Heart Circ Physiol Source Type: research

Cathepsin X promotes 6-hydroxydopamine-induced apoptosis of PC12 and SH-SY5Y cells.
Abstract The cysteine carboxypeptidase cathepsin X is an important player in degenerative processes under normal aging and pathological conditions. In the present study, we investigated the potential role of cathepsin X in 6-hydroxydopamine (6-OHDA)-induced toxicity in the pheochromocytoma cell line PC12 and neuroblastoma cell line SH-SY5Y. Cells exposed to 6-OHDA demonstrated alterations in the protein level of cathepsin X and activity of cathepsin X. Downregulation of cathepsin X expression by siRNA attenuated the neuronal death caused by 6-OHDA. Treatment with specific cathepsin X inhibitor AMS36 protected cell...
Source: Neuropharmacology - August 16, 2013 Category: Drugs & Pharmacology Authors: Pišlar AH, Zidar N, Kikelj D, Kos J Tags: Neuropharmacology Source Type: research

Curcumin analogue 1, 5-Bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one exhibit enhanced ability on Nrf2 activation and protection against acrolein-induced ARPE-19 cell toxicity.
Abstract Curcumin, a phytochemical agent in the spice turmeric, has received increasing attention for its anticancer, anti-inflammatory and antioxidant properties. However, application of curcumin have been limited due to its insolubility in water and poor bioavailability both clinically and experimentally. In addition, the protective effects and mechanisms of curcumin in eye diseases have been poorly studied. In the present study, we synthesized a curcumin analogue, 1, 5-Bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one (C3), which displayed improved protective effect against acrolein-induced toxicity in a human...
Source: Toxicology and Applied Pharmacology - August 13, 2013 Category: Toxicology Authors: Li Y, Zou X, Cao K, Xu J, Yue T, Dai F, Zhou B, Lu W, Feng Z, Liu J Tags: Toxicol Appl Pharmacol Source Type: research

Gestational diabetes impairs Nrf2-mediated adaptive antioxidant defenses and redox signaling in fetal endothelial cells in utero.
We examined the effects of GDM on the proteome, redox status and nuclear factor erythroid 2-related factor 2 (Nrf2) mediated antioxidant gene expression in human fetal endothelial cells. Proteomic analysis revealed that proteins involved in redox homeostasis were significantly altered in GDM and associated with increased mitochondrial superoxide generation, protein oxidation, DNA damage and diminished glutathione synthesis. In GDM cells, the lipid peroxidation product 4-hydroxynonenal (HNE) failed to induce nuclear Nrf2 accumulation and mRNA and/or protein expression of Nrf2 and its target genes NAD(P)H:quinone oxidoreduct...
Source: Diabetes - August 23, 2013 Category: Endocrinology Authors: Cheng X, Chapple SJ, Patel B, Puszyk W, Sudgen D, Yin X, Mayr M, Siow RC, Mann GE Tags: Diabetes Source Type: research

Mitochondrial fragmentation in cigarette smoke induced-bronchial epithelial cell senescence.
Conclusions: CSE-induced mitochondrial fragmentation is involved in cellular senescence through the mechanism of mitochondrial ROS production. Hence, disruption of mitochondrial dynamics may be a part of the pathogenic sequence of COPD development. PMID: 24056969 [PubMed - as supplied by publisher]
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - September 20, 2013 Category: Cytology Authors: Hara H, Araya J, Ito S, Kobayashi K, Takasaka N, Yoshii Y, Wakui H, Kojima J, Shimizu K, Numata T, Kawaishi M, Kamiya N, Odaka M, Morikawa T, Kaneko Y, Nakayama K, Kuwano K Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Α-synuclein and mitochondrial bioenergetics regulate tetrahydrobiopterin levels in a human dopaminergic model of PD.
Abstract Parkinson's disease (PD) is a multi-factorial disease resulting in preferential death of the dopaminergic neurons in the substantia nigra. Studies of PD-linked genes and toxin-induced models of PD have implicated mitochondrial dysfunction, oxidative stress and the misfolding and aggregation of α-synuclein (α-syn) as key factors in disease initiation and progression. Many of these features of PD may be modelled in cells or animal models using the neurotoxin 1-methyl-4-phenylpyridinium (MPP+). Reducing oxidative stress and NOS activity have been shown to be protective in cell or animal models of MPP+ toxi...
Source: Free Radical Biology and Medicine - October 19, 2013 Category: Biology Authors: Ryan BJ, Lourenço-Venda L, Crabtree MJ, Hale AB, Channon KM, Wade-Martins R Tags: Free Radic Biol Med Source Type: research

TRPML1 loss promotes production of reactive oxygen species: is oxidative damage a factor in mucolipidosis type IV?
TRPML1 is a lysosomal ion channel permeable to cations, including Fe2+. Mutations in MCOLN1, the gene coding for TRPML1, cause the lysosomal storage disease (LSD) Mucolipidosis type IV (MLIV). The role of TRPML1 in the cell is disputed and the mechanisms of cell deterioration in MLIV are unclear. The recent demonstration of Fe2+ buildup in MLIV cells raised the possibility that TRPML1 dissipates lysosomal Fe2+ and prevents its accumulation. Since Fe2+ catalyzes the production of reactive oxygen species (ROS), we set out to test whether or not the loss of TRPML1 promotes ROS production by Fe2�...
Source: BJ Cell - November 6, 2013 Category: Biochemistry Authors: J Coblentz, C St. Croix, K Kiselyov Tags: BJ Cell Source Type: research

Upregulation of mitochondrial Nox4 mediates TGF-β-induced apoptosis in cultured mouse podocytes.
Abstract Injury to podocyte leads to the onset of chronic renal diseases characterized by proteinuria. Elevated TGF-β in kidney tissue is associated with podocyte damage that ultimately results in apoptosis and detachment. We investigated the proapoptotic mechanism of TGF-β in immortalized mouse podocytes. Exogenous TGF-β1-induced podocyte apoptosis through caspase-3 activation which was related to elevated reactive oxygen species (ROS) levels generated by selective upregulation of Nox4. In mouse podocytes, Nox4 was predominantly localized to mitochondria and Nox4 upregulation by TGF-β1 markedly depolarized th...
Source: American Journal of Physiology. Renal Physiology - November 20, 2013 Category: Physiology Authors: Das R, Xu S, Quan X, Nguyen TT, Kong ID, Chung CH, Lee EY, Cha SK, Park KS Tags: Am J Physiol Renal Physiol Source Type: research

p62 Up-regulation Promotes Caspase-8 Activation Molecular Bases of Disease
Autophagy and apoptosis regulate cancer cell viability in response to cytotoxic stress; however, their functional relationship remains unclear. p62/sequestosome 1 is a multifunctional protein and a signaling hub that shuttles ubiquitinated proteins to the lysosome during autophagy. Autophagy inhibition up-regulates p62, and prior data suggest that p62 may mediate apoptosis. Here, we demonstrate that p62 can regulate a caspase-8-dependent apoptosis in response to the BH3 mimetic agent, ABT-263. Up-regulation of p62 was shown to enhance ABT-263-induced caspase-8 activation that was Bax-dependent and resulted from mitochondri...
Source: Journal of Biological Chemistry - November 22, 2013 Category: Chemistry Authors: Huang, S., Okamoto, K., Yu, C., Sinicrope, F. A. Tags: Cell Biology Source Type: research

High-content genome-wide RNAi screens identify regulators of parkin upstream of mitophagy
Nature advance online publication 24 November 2013. doi:10.1038/nature12748 Authors: Samuel A. Hasson, Lesley A. Kane, Koji Yamano, Chiu-Hui Huang, Danielle A. Sliter, Eugen Buehler, Chunxin Wang, Sabrina M. Heman-Ackah, Tara Hessa, Rajarshi Guha, Scott E. Martin & Richard J. Youle An increasing body of evidence points to mitochondrial dysfunction as a contributor to the molecular pathogenesis of neurodegenerative diseases such as Parkinson’s disease. Recent studies of the Parkinson’s disease associated genes PINK1 (ref. 2) and parkin (PARK2, ref. 3) indicate that they may act in a quality control pathway ...
Source: Nature AOP - November 24, 2013 Category: Research Authors: Samuel A. HassonLesley A. KaneKoji YamanoChiu-Hui HuangDanielle A. SliterEugen BuehlerChunxin WangSabrina M. Heman-AckahTara HessaRajarshi GuhaScott E. MartinRichard J. Youle Tags: Letter Source Type: research

Downregulation of PMCA2 increases the vulnerability of midbrain neurons to mitochondrial complex I inhibition.
Abstract Parkinson's disease is an age-associated disorder characterized by selective degeneration of dopaminergic neurons. The molecular mechanisms underlying the selective vulnerability of this subset of neurons are, however, not fully understood. Employing SH-SY5Y neuroblastoma cells and primary mesencephalic neurons, we here demonstrate a significant increase in cytosolic calcium after inhibition of mitochondrial complex I by means of MPP(+), which is a well-established environmental toxin-based in vitro model of Parkinson's disease. This increase in calcium is correlated with a downregulation of the neuron-sp...
Source: Neurotoxicology - November 21, 2013 Category: Neurology Authors: Brendel A, Renziehausen J, Behl C, Hajieva P Tags: Neurotoxicology Source Type: research

High-content genome-wide RNAi screens identify regulators of parkin upstream of mitophagy
tin & Richard J. Youle An increasing body of evidence points to mitochondrial dysfunction as a contributor to the molecular pathogenesis of neurodegenerative diseases such as Parkinson’s disease. Recent studies of the Parkinson’s disease associated genes PINK1 (ref. 2) and parkin (PARK2, ref. 3) indicate that they may act in a quality control pathway preventing the accumulation of dysfunctional mitochondria. Here we elucidate regulators that have an impact on parkin translocation to damaged mitochondria with genome-wide small interfering RNA (siRNA) screens coupled to high-content microscopy. Screening...
Source: Nature - November 24, 2013 Category: Research Authors: Samuel A. HassonLesley A. KaneKoji YamanoChiu-Hui HuangDanielle A. SliterEugen BuehlerChunxin WangSabrina M. Heman-AckahTara HessaRajarshi GuhaScott E. MartinRichard J. Youle Tags: Letter Source Type: research

A p38MAPK/MK2 signaling pathway leading to redox stress, cell death and ischemia/reperfusion injury
Conclusions: These data highlight a novel and important mechanism for p38MAPK to cause IRI and suggest it as a potential therapeutic target for prevention of tissue injury.
Source: Cell Communication and Signaling - January 14, 2014 Category: Molecular Biology Authors: Muhammad AshrafMatthias EbnerChristoph WallnerMartina HallerSana KhalidHubert SchwelbergerKatarzyna KozielMarion EnthammerMartin HermannStephan SickingerAfschin SoleimanChristina StegerStephanie VallantRobert SucherGerald BrandacherPeter SanterDuska Dragu Source Type: research