title: Effect of metabolic acidosis on the insulin-like growth factor-I system and cathepsins B and L gene expression in the kidney.
abstract: Prolonged acidemia causes growth retardation and muscle wasting, in part because of reduced food intake, depressed growth hormone secretion, and low serum insulin-like growth factor-I (IGF-I) levels. Paradoxically, in the rat kidney, protein synthesis increases, cathepsin B and L activities decline, protein degradation falls, and the kidneys enlarge. Because IGF-I has been implicated as a cause of renal hypertrophy in a variety of conditions, we examined whether IGF-I could be playing a role in the renal hypertrophy of acidosis. Rats were gavaged with NH4Cl or water for 4 days. Water-gavaged rats either were pair-fed with the NH4Cl-loaded rats (pH 7.15) or were given free access to food and served as controls. After 2 days, kidney weight and IGF-I mRNA levels did not differ between the groups, but kidney IGF-I protein levels were significantly higher in the acidotic rats. After 4 days the kidneys of the acidotic rats were significantly larger than the kidneys in both control groups but the renal IGF-I levels did not differ between the groups. It is notable that renal cathepsin B and L mRNA levels were reduced by 30% to 50% at both times. Thus the transient increase in renal IGF-I protein levels in acidosis, before the onset of hypertrophy, suggests that IGF-I may play a role in initiating kidney growth. Furthermore, it appears that reduced cathepsin B and L gene expression is a cause of the low renal cathepsin activity seen in acidosis. This likely contributes to the depressed renal proteolysis caused by acidosis.
authors: Veterans Affairs Palo Alto Health Care System and the Department of Medicine, Stanford University, California, USA.
authors: J
authors: J
authors: Fawcett
authors: F W
authors: FW
authors: Hsu
authors: T
authors: T
authors: Tsao
authors: R
authors: R
authors: Rabkin
mesh_terms: D000136:Acid-Base Equilibrium; D000138:Acidosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002401:Cathepsin B / Q000235:genetics*; D056668:Cathepsin L; D002403:Cathepsins / Q000235:genetics*; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D005260:Female; D015870:Gene Expression; D013006:Growth Hormone / Q000235:genetics; D006984:Hypertrophy; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000235:genetics
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D017526:Receptor, IGF Type 1; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L; C534280:Ctsl protein, rat