Protein Streptozotocin

It is generally assumed that the toxicity of streptozotocin is dependent upon the DNA alkylating activity of its methylnimethylnitrosourea moiety, especially at the O6 position of guanine. The transfer of the methyl group from streptozotocin to the DNA molecule causes damage, which along a defined chain of events, results in the fragmentation of the DNA. Protein glycosylation may be an additional damaging factor . In the attempt to repair DNA, poly(ADP-ribose) polymerase (PARP) is overstimulated. This diminishes cellular NAD+, and subsequently ATP, stores the depletion of the cellular energy stores ultimately results in beta cell necrosis. Although streptozotocin also methylates proteins ,DNA methylation is ultimately responsible for beta cell death, but it is likely that protein methylation contributes to the functional defects of the beta cells after exposure to streptozotocin. Inhibitors of poly ADP-ribosylation suppress the process of DNA methylation. Thus, injection of nicotinamide
2) and can liberate NO. In fact, streptozotocin has been shown to increase the activity of guanylyl cyclase and the formation of cGMP, which are characteristic effects of NO. However, the alkylating agent methyl methanesulphonate is the most toxic compound, though unlike MNU, it is not a NO donor ,indicating that NO is not an indispensable prerequisite for the toxic action of the family of alkylating agents that streptozotocin belongs to. Finally, some minor generation of ROS, including superoxide and hydroxyl radicals originating from hydrogen peroxide dismutation during hypoxanthine metabolism may accompany the effect of streptozotocin and accelerate the process of beta cell destruction but ROS do not play a crucial