Extrahepatic expression of P450 proteins in insulin-dependent diabetes mellitus.
1. Male Wistar rats were rendered diabetic by the administration of a single intraperitoneal dose of streptozotocin; the levels of the xenobiotic-inducible P450 proteins were determined in the lung and kidney using diagnostic substrates and immunoblotting employing polyclonal antibodies. The glutathione conjugation system in the cytosol of these tissues was also investigated. 2. The onset of insulin-dependent diabetes did not influence the O-dealkylations of methoxyresorufin, ethoxyresorufin and pentoxyresorufin in either kidney or lung. 3. Lauric acid hydroxylase activity, however, was induced in the kidney but no activity was detectable in the lung. Immunoblot analysis of kidney microsomes using antibodies to P4504A1 revealed the presence of two bands, both of which were clearly inducible in diabetes. In pulmonary microsomes a single faint band was detected which also appeared to be higher in the diabetic rats. 4. Aniline p-hydroxylase activity was not detectable in the kidney, but activity was measurable in the lung and was suppressed in diabetes. Immunoblot analysis of pulmonary microsomes using antibodies to P4502E1 immunodetected a single band which was suppressed in diabetes. In the kidney microsomes a single band was also detected which was, however, markedly elevated in diabetes. 5. Glutathione S-transferase activity was modestly higher in the kidney, but not lung, of the diabetic animals. Glutathione reductase and total glutathione levels were not influenced by the presence of diabetes. 6. It is concluded that streptozotocin-induced insulin-dependent diabetes modulates extrahepatic P450 proteins, the effect being both tissue- and isoform-specific.
Irizar
A
A
Group, School of Biological Sciences, University of Surrey, Guildford, UK.
Ioannides
C
C
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology*; D004797:Enzyme-Linked Immunosorbent Assay; D005982:Glutathione Transferase / Q000032:analysis; D007668:Kidney / Q000201:enzymology* / Q000648:ultrastructure; D008168:Lung / Q000201:enzymology* / Q000648:ultrastructure; D008297:Male; D008861:Microsomes / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar
D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase