AJP - Cell Physiology, Vol 260, Issue 2 C277-C282, Copyright © 1991 by American Physiological Society

ARTICLES

Abnormalities in protein synthesis and degradation induced by extracellular pH in BC3H1 myocytes

B. K. England, J. L. Chastain and W. E. Mitch
Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322.

Metabolic acidosis impairs protein and amino acid metabolism in rat muscle. To examine how extracellular acidification affects cellular protein turnover, we studied the BC3H1 myocyte. At pH 7.1 vs. 7.4, intracellular pH was lower; the decrease was greater in cells incubated in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-tris(hydroxymethyl)aminomethane compared with bicarbonate buffer. We monitored degradation of proteins labeled with L-[14C]phenylalanine by measuring radioactivity released into media containing an excess of unlabeled phenylalanine. Extracellular acidification increased degradation compared with incubation at pH 7.4. Adding a physiological concentration of insulin (1 nM) decreased protein degradation at pH 7.1 and 7.4; a supraphysiological (71 nM) insulin concentration decreased degradation at pH 7.1 to the same rate as cells incubated at pH 7.4 without insulin. Compared with pH 7.4, protein synthesis decreased 29% at pH 7.2; at pH 7.6 it increased 129%. Insulin stimulated protein synthesis at all pHs, but at pH 7.4 the insulin-induced increase was less than the rate at pH 7.6 without insulin. Dexamethasone did not change protein breakdown regardless of the pH; it had variable effects on protein synthesis. Thus extracellular acidification causes marked changes in protein turnover in BC3H1 myocytes.

This article has been cited by other articles:

				H. A. Franch, S. Raissi, X. Wang, B. Zheng, J. L. Bailey, and S. R. Price Acidosis impairs insulin receptor substrate-1-associated phosphoinositide 3-kinase signaling in muscle cells: consequences on proteolysis Am J Physiol Renal Physiol, October 1, 2004; 287(4): F700 - F706. [Abstract] [Full Text] [PDF]

				G. Caso, B. A. Garlick, G. A. Casella, D. Sasvary, and P. J. Garlick Acute metabolic acidosis inhibits muscle protein synthesis in rats Am J Physiol Endocrinol Metab, July 1, 2004; 287(1): E90 - E96. [Abstract] [Full Text] [PDF]

				W. E. Mitch Insights into the Abnormalities of Chronic Renal Disease Attributed to Malnutrition J. Am. Soc. Nephrol., January 1, 2002; 13(90001): S22 - 27. [Abstract] [Full Text] [PDF]

				X. Wang, J. M. Chinsky, P. A. Costeas, and S. R. Price Acidification and glucocorticoids independently regulate branched-chain {alpha}-ketoacid dehydrogenase subunit genes Am J Physiol Cell Physiol, May 1, 2001; 280(5): C1176 - C1183. [Abstract] [Full Text] [PDF]

				W. E. Mitch, J. L. Bailey, X. Wang, C. Jurkovitz, D. Newby, and S. R. Price Evaluation of signals activating ubiquitin-proteasome proteolysis in a model of muscle wasting Am J Physiol Cell Physiol, May 1, 1999; 276(5): C1132 - C1138. [Abstract] [Full Text] [PDF]

				H. J. Adrogue and N. E. Madias Management of Life-Threatening Acid-Base Disorders- First of Two Parts N. Engl. J. Med., January 1, 1998; 338(1): 26 - 34. [Full Text] [PDF]