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Mitochondrial function contributes to oxysterols-induced osteogenic differentiation in mouse embryonic stem cells
This study investigated the effect of an oxysterol combination of 22(S)-hydroxycholesterol and 20(S)-hydroxycholesterol (SS) on osteogenic differentiation of ESCs and the alterations to mitochondrial activity during differentiation. Osteogenic differentiation was assessed by alkaline phosphatase (ALP) activity, matrix mineralization, mRNA expression of osteogenic factors, runt-related transcription factor 2, osterix, and osteocalcin, and protein levels of collagen type IA (COLIA) and osteopontin (OPN). Treatment of cells with SS increased osteoinductive activity compared to the control group. Intracellular reactive oxygen ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - December 16, 2014 Category: Molecular Biology Source Type: research

Downregulation of diacylglycerol kinase ζ enhances activation of cytokine-induced NF-κB signaling pathway
This study shows that siRNA-mediated DGKζ knockdown in HeLa cells facilitates degradation of IκB, followed by nuclear translocation of NF-κB p65 subunit. In addition, DGKζ-deficient MEFs show upregulation of p65 subunit phosphorylation at Serine 468 and 536 and its interaction with CBP transcriptional coactivator upon TNF-α stimulation. These modifications of p65 subunit might engender enhanced NF-κB transcriptional reporter assay of DGKζ knockdown cells. These findings provide further insight into the regulatory mechanisms of cytokine-induced NF-κB activation.
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - December 5, 2014 Category: Molecular Biology Source Type: research

CSN-associated USP48 confers stability to nuclear NF-κB/RelA by trimming K48-linked Ub-chains
In this study we observed that USP48, a DUB of hitherto ill-defined function identified through a siRNA screen, associates with the CSN and RelA in the nucleus. We show that USP48 trims rather than completely disassembles long K48-linked free and substrate-anchored Ub-chains, a catalytic property only shared with ataxin-3 (Atx3) and otubain-1 (OTU1), and that USP48 Ub-chain-trimming activity is regulated by casein-kinase-2 (CK2)-mediated phosphorylation in response to cytokine-stimulation. Functionally, we demonstrate for the first time the CSN and USP48 to cooperatively stabilize the nuclear pool of RelA, thereby facilita...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - December 5, 2014 Category: Molecular Biology Source Type: research

Novel role for TRPC4 in regulation of macroautophagy by a small molecule in vascular endothelial cells
In this study, we identified trans-3,5,4′-trimethoxystilbene (TMS) as a potent small molecule inducer of autophagy in human umbilical vascular endothelial cells (HUVECs) in the presence of serum. Using high-throughput DNA microarray and siRNA transfection technologies, we demonstrated that TMS induced autophagy by up-regulating the expression of the transient receptor potential canonical channel 4 (TRPC4), an important cation channel in HUVECs. In addition, the overexpression of TRPC4 by plasmid transfection also induced autophagy. Mechanistic studies revealed that the up-regulation of TRPC4 increased the intracellular C...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - December 4, 2014 Category: Molecular Biology Source Type: research

Ki-1/57 and CGI-55 ectopic expression impact cellular pathways involved in proliferation and stress response regulation
Publication date: December 2014 Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1843, Issue 12 Author(s): Fernanda C. Costa , Ângela Saito , Kaliandra A. Gonçalves , Pedro M. Vidigal , Gabriela V. Meirelles , Gustavo C. Bressan , Jörg Kobarg Ki-1/57 (HABP4) and CGI-55 (SERBP1) are regulatory proteins and paralogs with 40.7% amino acid sequence identity and 67.4% similarity. Functionally, they have been implicated in the regulation of gene expression on both the transcriptional and mRNA metabolism levels. A link with tumorigenesis is suggested, since both paralogs show altered expression le...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - November 11, 2014 Category: Molecular Biology Source Type: research

Involvement of store-operated Ca2+ entry in activation of AMP-activated protein kinase and stimulation of glucose uptake by M3 muscarinic acetylcholine receptors in human neuroblastoma cells
Publication date: December 2014 Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1843, Issue 12 Author(s): Maria C. Olianas , Simona Dedoni , Pierluigi Onali Gq/11-coupled muscarinic acetylcholine receptors (mAChRs) belonging to M1, M3 and M5 subtypes have been shown to activate the metabolic sensor AMP-activated protein kinase (AMPK) through Ca2+/calmodulin-dependent protein kinase kinase-β (CaMKKβ)-mediated phosphorylation at Thr172. However, the source of Ca2+ required for this response has not been yet elucidated. Here, we investigated the involvement of store-operated Ca2+ entry (SOCE) ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - November 11, 2014 Category: Molecular Biology Source Type: research

CRNDE, a long non-coding RNA responsive to insulin/IGF signaling, regulates genes involved in central metabolism
Publication date: February 2014 Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1843, Issue 2 Author(s): Blake C. Ellis , Lloyd D. Graham , Peter L. Molloy Colorectal neoplasia differentially expressed (CRNDE) is a novel gene that is activated early in colorectal cancer but whose regulation and functions are unknown. CRNDE transcripts are recognized as long non-coding RNAs (lncRNAs), which potentially interact with chromatin-modifying complexes to regulate gene expression via epigenetic changes. Complex alternative splicing results in numerous transcripts from this gene, and we have identifie...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - November 1, 2014 Category: Molecular Biology Source Type: research

NADPH oxidase subunit p22phox-mediated reactive oxygen species contribute to angiogenesis and tumor growth through AKT and ERK1/2 signaling pathways in prostate cancer
In this study, we reported that levels of ROS and p22phox expression are greatly increased in human prostate cancer tissues, and knockdown of p22phox by specific small interfering RNA (siRNA) decreased ROS levels in prostate cancer cells. We also showed that stable downregulation of p22phox in prostate cancer cells inhibited cell proliferation and colony formation, which was mediated by AKT and extracellular signal-regulated kinase (ERK)1/2 signaling pathways and their downstream molecules hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF). The NADPH oxidase subunit NOX1 was also elevated ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - November 1, 2014 Category: Molecular Biology Source Type: research

Poly(ADP-ribose) polymerase 1 inhibition protects against low shear stress induced inflammation
Conclusions: LSS induced oxidative damage and PARP-1 activation via MEK/ERK pathway. PARP-1 inhibition restored Sirt1 activity by increasing NAD+ level and decreased iNOS and ICAM-1 expression by inhibiting NF-κB nuclear translocation and activity as well as NF-κB phosphorylation. PARP-1 played a fundamental role in LSS induced inflammation. Inhibition of PARP-1 might be a mechanism for treatment of inflammation response during atherosclerosis. Highlights ► We firstly demonstrated the critical role of PARP-1 in low shear stress induced inflammation. ► Low shear stress increased superoxide production and nitrotyrosine...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - November 1, 2014 Category: Molecular Biology Source Type: research

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