Oxidants and Ca+2 induce PGC-1alpha degradation through calpain.

Archives of Biochemistry and Biophysics
Kyle A RasbachRick G Schnellmann

Abstract

Peroxisome proliferator activator receptor gamma coactivator 1alpha (PGC-1alpha) is a transcriptional coactivator known to mediate mitochondrial biogenesis. Whereas PGC-1alpha transcription is regulated by a variety of signaling cascades, the mechanisms of PGC-1alpha degradation have received less investigation. Thus, we investigated the mechanisms responsible for PGC-1alpha degradation in renal proximal tubular cells (RPTC). Amino acid sequence analysis of the PGC-1alpha protein revealed three PEST sequence-rich regions, predictive of proteolysis by calpains and/or the proteasome. Under basal conditions, treatment with the protein synthesis inhibitor cycloheximide resulted in rapid degradation of PGC-1alpha (t(1/2)=38 min), which was blocked by the proteasome inhibitor epoxomicin, but not the calpain inhibitor calpeptin. Oxidant exposure resulted in the degradation of both endogenous and adenovirally over-expressed PGC-1alpha, which was inhibited by calpeptin but not epoxomicin. Thapsigargin-induced release of ER Ca(2+) also stimulated calpain-dependent, epoxomicin-independent degradation of PGC-1alpha. Finally, Ca(2+) addition to lysates of RPTC over-expressing PGC-1alpha resulted in calpeptin-sensitive, epoxomicin-insensitiv...Continue Reading

References

Jan 31, 1992·Biochemical and Biophysical Research Communications·M HayashiS Kawashima
Dec 29, 1989·Biochemical and Biophysical Research Communications·R Siman, G Christoph
Dec 15, 1994·Annals of the New York Academy of Sciences·R A NixonM Beermann
Jun 25, 1996·Proceedings of the National Academy of Sciences of the United States of America·K K WangP Yuen
Jan 1, 1996·Advances in Experimental Medicine and Biology·K K Wang Yuen P-W
Dec 1, 1996·The American Journal of Physiology·G Nowak, R G Schnellmann
Nov 21, 1997·Biochemical and Biophysical Research Communications·S L WatersR G Schnellmann
May 28, 1998·The Journal of Biological Chemistry·H LiuJ L Stevens
Sep 1, 1999·Proceedings of the National Academy of Sciences of the United States of America·L MengC M Crews
Oct 16, 1999·The Journal of Biological Chemistry·S D ShumwayS Miyamoto
Jun 8, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·K SchwarzM Groettrup
Aug 27, 2003·Nature·Konrad T HowitzDavid A Sinclair
Jan 30, 2004·Diabetes·Koichi SuzukiHiroyuki Sorimachi
Feb 28, 2004·The Journal of Biological Chemistry·Peter TompaPeter Friedrich
Jul 16, 2004·Kidney International·Wayel Jassem, Nigel D Heaton
Dec 31, 2004·American Journal of Physiology. Renal Physiology·Thorsten FeldkampJoel M Weinberg
Feb 18, 2005·The Journal of Biological Chemistry·Shino NemotoToren Finkel
Apr 15, 2005·Redox Report : Communications in Free Radical Research·Yi Zheng, Xun Shen
Apr 28, 2005·Free Radical Biology & Medicine·Manya Dhar-MascareñoDavid W Golde
Aug 12, 2005·Annals of the New York Academy of Sciences·Henry M HondaJames N Weiss
Feb 25, 2006·Cardiovascular Research·Fabio Di Lisa, Paolo Bernardi
Jun 23, 2006·American Journal of Physiology. Cell Physiology·David D ArringtonRick G Schnellmann
Nov 23, 2006·The Journal of Biological Chemistry·Kyle A Rasbach, Rick G Schnellmann
Feb 20, 2007·Biochemical and Biophysical Research Communications·Kyle A Rasbach, Rick G Schnellmann
Apr 4, 2007·Genes & Development·Christoph HandschinBruce M Spiegelman
Feb 13, 2008·The Journal of Pharmacology and Experimental Therapeutics·Kyle A Rasbach, Rick G Schnellmann
Mar 5, 2008·Toxicology and Applied Pharmacology·Khadidja HaidaraDiana A Averill-Bates
Mar 19, 2008·Proceedings of the National Academy of Sciences of the United States of America·Zoltan AranyBruce M Spiegelman

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Citations

Dec 15, 2010·The Journal of Biological Chemistry·Tanu RanaGautam Chaudhuri
Jan 28, 2010·The Journal of Pharmacology and Experimental Therapeutics·Jason A FunkRick G Schnellmann
Jan 26, 2012·American Journal of Physiology. Endocrinology and Metabolism·Zhiyou ZhangJason K Kim
Jul 26, 2011·Journal of the American Society of Nephrology : JASN·Fionnuala B HickeyMadeline Murphy
Mar 5, 2016·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Vu Thi ThuJin Han

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