Mcl-1 Degradation during Hepatocyte Lipoapoptosis

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Mcl-1 degradation during hepatocyte lipoapoptosis.

The mechanisms of free fatty acid-induced lipoapoptosis are incompletely understood. Here we demonstrate that Mcl-1, an anti-apoptotic member of the Bcl-2 family, was rapidly degraded in hepatocytes in response to palmitate and stearate by a proteasome-dependent pathway. Overexpression of a ubiquitin-resistant Mcl-1 mutant in Huh-7 cells attenuated palmitate-mediated Mcl-1 loss and lipoapoptosi...

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Degradation of cIAPs contributes to hepatocyte lipoapoptosis.

Hepatocyte apoptosis is a hallmark of nonalcoholic steatohepatitis. We have previously observed that the saturated free fatty acids (FFAs) induce hepatocyte apoptosis in part via a death receptor 5 (DR5)-mediated signaling pathway. Cellular inhibitor of apoptosis protein 1 and 2 (cIAP-1 and cIAP-2) proteins are potent inhibitors of death receptor-mediated apoptosis. However, the role of the cIA...

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Death receptor 5 signaling promotes hepatocyte lipoapoptosis.

Nonalcoholic steatohepatitis is characterized by hepatic steatosis, elevated levels of circulating free fatty acids (FFA), endoplasmic reticulum (ER) stress, and hepatocyte lipoapoptosis. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor 5 (DR5) is significantly elevated in patients with nonalcoholic steatohepatitis, and steatotic hepatocytes demonstrate increased s...

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Mechanisms of lysophosphatidylcholine-induced hepatocyte lipoapoptosis.

Isolated hepatocytes undergo lipoapoptosis, a feature of hepatic lipotoxicity, on treatment with saturated free fatty acids (FFA) such as palmitate (PA). However, it is unknown if palmitate is directly toxic to hepatocytes or if its toxicity is indirect via the generation of lipid metabolites such as lysophosphatidylcholine (LPC). PA-mediated hepatocyte lipoapoptosis is associated with endoplas...

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CALL FOR PAPERS Physiology and GI Cancer Degradation of cIAPs contributes to hepatocyte lipoapoptosis

Akazawa Y, Guicciardi ME, Cazanave SC, Bronk SF, Werneburg NW, Kakisaka K, Nakao K, Gores GJ. Degradation of cIAPs contributes to hepatocyte lipoapoptosis. Am J Physiol Gastrointest Liver Physiol 305: G611–G619, 2013. First published September 5, 2013; doi:10.1152/ajpgi.00111.2013.—Hepatocyte apoptosis is a hallmark of nonalcoholic steatohepatitis. We have previously observed that the saturated...

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ژورنال

عنوان ژورنال: Journal of Biological Chemistry

سال: 2009

ISSN: 0021-9258

DOI: 10.1074/jbc.m109.039545