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Full-Text Articles in Medicine and Health Sciences
A Role For Mir-296 In The Regulation Of Lipoapoptosis By Targeting Puma., Sophie C. Cazanave, Justin L. Mott, Nafisa A. Elmi, Steven F. Bronk, Howard C. Masuoka, Michael R. Charlton, Gregory J. Gores
A Role For Mir-296 In The Regulation Of Lipoapoptosis By Targeting Puma., Sophie C. Cazanave, Justin L. Mott, Nafisa A. Elmi, Steven F. Bronk, Howard C. Masuoka, Michael R. Charlton, Gregory J. Gores
Journal Articles: Biochemistry & Molecular Biology
Saturated free fatty acids (FFA) induce hepatocyte lipoapoptosis, a key mediator of liver injury in nonalcoholic fatty liver disease (NAFLD). Lipoapoptosis involves the upregulation of the BH3-only protein PUMA, a potent pro-apoptotic protein. Given that dysregulation of hepatic microRNA expression has been observed in NAFLD, we examined the role of miRNA in regulating PUMA expression during lipotoxicity. By in silico analysis, we identified two putative binding sites for miR-296-5p within the 3' untranslated region (UTR) of PUMA mRNA. Enforced miR-296-5p levels efficiently reduced PUMA protein expression in Huh-7 cells, while antagonism of miR-296-5p function increased PUMA cellular levels. Reporter gene …
Noxa Mediates Hepatic Stellate Cell Apoptosis By Proteasome Inhibition., Ivette M. Sosa Seda, Justin L. Mott, Yuko Akazawa, Fernando J. Barreyro, Steven F. Bronk, Scott H. Kaufmann, Gregory J. Gores
Noxa Mediates Hepatic Stellate Cell Apoptosis By Proteasome Inhibition., Ivette M. Sosa Seda, Justin L. Mott, Yuko Akazawa, Fernando J. Barreyro, Steven F. Bronk, Scott H. Kaufmann, Gregory J. Gores
Journal Articles: Biochemistry & Molecular Biology
Aim: Induction of hepatic stellate cell (HSC) apoptosis is a viable therapeutic strategy to reduce liver fibrogenesis. Although BH3-only proteins of the Bcl-2 family trigger pro-apoptotic pathways, the BH3-only proteins mediating HSC apoptosis have not been well defined. Our aim, using proteasome inhibition as a model to induce HSC apoptosis, was to examine the BH3-only proteins contributing to cell death of this key liver cell subtype. Methods: Apoptosis was induced by treating LX-2 cells, an immortalized human hepatic stellate cell line, and primary rat stellate cells with the proteasome inhibitor MG-132. Results: Treatment with proteasome inhibitors increased expression of Noxa …