Free Fatty Acids Induce JNK-dependent Hepatocyte Lipoapoptosis
作者： Harmeet Malhi , Steven F. Bronk , Nathan W. Werneburg , Gregory J. Gores
关键词:
摘要: Elevated serum free fatty acids (FFAs) and hepatocyte lipoapoptosis are features of non-alcoholic liver disease. However, the mechanism by which FFAs mediate is unclear. Because JNK activation pivotal in both metabolic syndrome accompanying disease cellular apoptosis, we examined role FFA-induced lipoapoptosis. Multiple cell lines primary mouse hepatocytes were treated culture with monounsaturated saturated acids. Despite equal steatosis, apoptosis greater during exposure to versus FFAs. Inhibition JNK, pharmacologically as well genetically, reduced FFA-mediated Cell death was caspase-dependent associated mitochondrial membrane depolarization cytochrome c release indicating pathway apoptosis. JNK-dependent Bax, a known mediator dysfunction. As can activate Bim, BH3 domain-only protein capable binding activating its also examined. Small interfering RNA-targeted knock-down Bim attenuated Bax death. Collectively data indicate that induce proapoptotic Bcl-2 proteins trigger apoptotic pathway.
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Seon-Hee Oh, Ki-Jung Yun, Ji-Xing Nan, Dong-Hwan Sohn, Byung-Hoon Lee, Changes in expression and immunolocalization of protein associated with toxic bile salts-induced apoptosis in rat hepatocytes. Archives of Toxicology. ,vol. 77, pp. 110- 115 ,(2003) , 10.1007/S00204-002-0415-X
Charles A. Harris, Eugene M. Johnson, BH3-only Bcl-2 family members are coordinately regulated by the JNK pathway and require Bax to induce apoptosis in neurons. Journal of Biological Chemistry. ,vol. 276, pp. 37754- 37760 ,(2001) , 10.1074/JBC.M104073200
Sho-ichi Yamagishi, Tamami Okamoto, Shinjiro Amano, Yosuke Inagaki, Kohachiro Koga, Mari Koga, Hiroshi Choei, Nobuyuki Sasaki, Seiji Kikuchi, Masayoshi Takeuchi, Zenji Makita, Palmitate-induced apoptosis of microvascular endothelial cells and pericytes. Molecular Medicine. ,vol. 8, pp. 179- 184 ,(2002) , 10.1007/BF03402010
Shane R. Bruckner, Steven P. Tammariello, Chia-Yi Kuan, Richard A. Flavell, Pasko Rakic, Steven Estus, JNK3 contributes to c-Jun activation and apoptosis but not oxidative stress in nerve growth factor-deprived sympathetic neurons. Journal of Neurochemistry. ,vol. 78, pp. 298- 303 ,(2001) , 10.1046/J.1471-4159.2001.00400.X
Mark J Czaja, Hailing Liu, Yongjun Wang, Oxidant-induced hepatocyte injury from menadione is regulated by ERK and AP-1 signaling. Hepatology. ,vol. 37, pp. 1405- 1413 ,(2003) , 10.1053/JHEP.2003.50233
Hideaki Kaneto, Yoshihisa Nakatani, Takeshi Miyatsuka, Dan Kawamori, Taka-aki Matsuoka, Munehide Matsuhisa, Yoshitaka Kajimoto, Hidenori Ichijo, Yoshimitsu Yamasaki, Masatsugu Hori, Possible novel therapy for diabetes with cell-permeable JNK-inhibitory peptide Nature Medicine. ,vol. 10, pp. 1128- 1132 ,(2004) , 10.1038/NM1111
Esther BE Becker, Jenny Howell, Yuki Kodama, Philip A Barker, Azad Bonni, Characterization of the c-Jun N-Terminal Kinase-BimEL Signaling Pathway in Neuronal Apoptosis The Journal of Neuroscience. ,vol. 24, pp. 8762- 8770 ,(2004) , 10.1523/JNEUROSCI.2953-04.2004
C MATTEONI, Z YOUNOSSI, T GRAMLICH, N BOPARAI, Y LIU, A MCCULLOUGH, Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. ,vol. 116, pp. 1413- 1419 ,(1999) , 10.1016/S0016-5085(99)70506-8
Ariel E. Feldstein, Nathan W. Werneburg, Ali Canbay, Maria Eugenia Guicciardi, Steven F. Bronk, Robert Rydzewski, Laurence J. Burgart, Gregory J. Gores, Free fatty acids promote hepatic lipotoxicity by stimulating TNF‐α expression via a lysosomal pathway Hepatology. ,vol. 40, pp. 185- 194 ,(2004) , 10.1002/HEP.20283
Thomas L Deckwerth, Jeffrey L Elliott, C.Michael Knudson, Eugene M Johnson, William D Snider, Stanley J Korsmeyer, BAX is required for neuronal death after trophic factor deprivation and during development Neuron. ,vol. 17, pp. 401- 411 ,(1996) , 10.1016/S0896-6273(00)80173-7