Mechanism of induction of cytochrome P-450ac (P-450j) in chemically induced and spontaneously diabetic rats.
Previous studies demonstrated that a microsomal high-affinity N-nitrosodimethylamine demethylase activity and cytochrome P-450ac (an acetone/ethanol-inducible form) were induced by streptozotocin-induced diabetes in rats. In the present work, the induction was studied in detail in two chemically induced (by streptozotocin and alloxan) diabetic rat models and one spontaneously (BB/Wor) diabetic rat model. All the diabetic conditions caused increases in three parameters: (a) microsomal N-nitrosodimethylamine demethylase activity which is known to be a good indicator of the level of P-450ac; (b) the levels of P-450ac as determined by immunoblot analysis; and (c) the levels of mRNA of P-450ac as determined by hybridization assays with a cDNA probe for this enzyme. These increases were abolished by treatment of the diabetic rats with insulin. The results suggest that the pathophysiological condition of diabetes is responsible for the induction of P-450ac and elevation of mRNA is involved in all of the three diabetic models investigated.
Dong
Z G
ZG
Department of Biochemistry, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103-2757.
Hong
J Y
JY
Ma
Q A
QA
Li
D C
DC
Bullock
J
J
Gonzalez
F J
FJ
Park
S S
SS
Gelboin
H V
HV
Yang
C S
CS
D000818:Animals; D000911:Antibodies, Monoclonal; D001835:Body Weight; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology*; D004790:Enzyme Induction; D007328:Insulin / Q000627:therapeutic use; D007527:Isoenzymes / Q000096:biosynthesis*; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000911:Antibodies, Monoclonal; D007328:Insulin; D007527:Isoenzymes; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System