Decreased activity and impaired induction of nitric oxide synthase by lipopolysaccharides in streptozotocin-induced diabetic rats.
The effect of diabetes was determined on nitric oxide synthase (NOS) activity in rat heart and liver. The diabetes was induced by streptozotocin (STZ) and NOS activity was determined after 1 or 12 weeks post-STZ injection. In both tissues, the majority of NOS activity was associated with endothelial constitutive calcium-sensitive NOS (ecNOS) isoform and found in the particulate (100,000xg pellet) fraction in young rats. The diabetes as well as age reduced this activity significantly in heart, whereas only the age caused a decrease in ecNOS activity in liver tissue. Lipopolysaccharides (LPS) induced calcium-insensitive iNOS activity in both young and old rats. The induction was significantly higher (up to 10-fold) in liver as compared to heart. Although the maximum induction of iNOS in young rats was almost similar in diabetic tissues as compared to control animals, there was a lag period for induction of iNOS in diabetic tissues. In old diabetic rats, the induction by LPS was almost completely abolished. These results suggest that diabetes causes either no change or a decrease in ecNOS activity and impairment in the induction of iNOS by LPS in rat heart and liver.
Khandelwal
Ramji L
RL
Department of Biochemistry, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan, Canada S7N 5E5. ramji.khandelwal@usask.ca
Gupta
Dhananjay
D
Sulakhe
Prakash V
PV
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013997:Time Factors
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat