Necessary but not sufficient: the role of glucocorticoids in the acidosis-induced increase in levels of mRNAs encoding proteins of the ATP-dependent proteolytic pathway in rat muscle.
Muscle protein degradation is accelerated by the acidosis associated with chronic renal failure. In isolated muscles from acidotic rats, a cytosolic, ATP-dependent proteolytic pathway is stimulated with a concurrent increase in the abundance of mRNAs encoding ubiquitin and subunits of the 26S proteasome complex associated with this degradative pathway. Adrenalectomy (ADX) prevents the acidosis-induced increase in muscle protein degradation unless high physiologic doses of glucocorticoids are administered to acidotic, adrenalectomized rats. We have examined the roles that acidosis and glucocorticoids have in the increase in mRNAs encoding proteins of the ATP-dependent-ubiquitin-proteasome proteolytic pathway in ADX rats. We found that ubiquitin and proteasome C2 and C9 subunit mRNA levels are increased in the white fiber, extensor digitorus longus (EDL) and mixed fiber, gastrocnemius muscles from acidotic ADX rats that received dexamethasone whereas acidosis alone or dexamethasone alone failed to increase these mRNAs. In contrast, acidosis plus dexamethasone decreased the total RNA content in both muscles. These data suggest that in muscle, the response to acidosis involves the specific activation of the ATP-ubiquitin-proteasome proteolytic pathway. Moreover, glucocorticoids are required but not directly responsible for the acidosis-induced increase in the mRNAs encoding proteins of this degradative pathway.
Price
S R
SR
Renal Division, Emory University School of Medicine, Atlanta, Ga. 30322, USA.
Bailey
J L
JL
England
B K
BK
D000138:Acidosis / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000315:Adrenalectomy; D000818:Animals; D003546:Cysteine Endopeptidases / Q000096:biosynthesis*; D010450:Endopeptidases / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology / Q000502:physiology*; D009097:Multienzyme Complexes / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014158:Transcription, Genetic; D014452:Ubiquitins / Q000097:blood*
D005938:Glucocorticoids; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D014452:Ubiquitins; D000255:Adenosine Triphosphate; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex