Proteasome activity in experimental diabetes

Abstract

Numerous studies have indicated that oxidative stress contributes to the development and progression of diabetes and other related complications. Since the ubiquitin-proteasome pathway is involved in degradation of oxidized proteins, it is to be expected that alterations in proteasomedependent proteolysis accompany diabetes. This paper focuses on the role of the proteasome in alloxaninduced experimental diabetes. The changes in proteasomal activity and oxidative stress indices (protein oxidation and lipid peroxidation) were evaluated. The obtained results revealed increased protein oxidation and lipid peroxidation, as well as alterations in proteasomal activities in diabetic rats. Our data indicates a significant decrease in chymotryptic-like activity; increased tryptic-like activity; and unchanged post-glutamyl peptide hydrolytic-like activity. These findings suggest the presence of oxidative stress in diabetes that appears to result in changes to the ubiquitin-proteasome pathway.

Increased 4‐hydroxy‐2‐nonenal‐induced proteasome dysfunction is correlated with cardiac damage in streptozotocin‐injected rats with isoproterenol infusion

“…Proteolytic inactivity in proteasomes was a direct consequence of oxidative stress or a result of other diabetes‐related metabolic alterations, assigning a definite role for proteasomal activities in the genesis and progression of diabetic cardiac complications. The ubiquitin–proteasome system becomes dysfunctional during long‐term hyperglycaemia . In earlier studies, we and others showed that cardiac 4HNE levels were increased in both type 1 and type 2 diabetes .…”

“…First, increased 4HNE adduct formation with the mitochondrial respiratory complex 2 protein succinate dehydrogenase was reported in the heart tissue by Lashin et al . Second, 4HNE‐induced mitochondrial damage in the diabetic heart has been widely reported; however, only a few studies determined the role of 4HNE in other subcellular organelles like the proteasome in diabetic cardiomyopathy …”

“…27 First, increased 4HNE adduct formation with the mitochondrial respiratory complex 2 protein succinate dehydrogenase was reported in the heart tissue by Lashin et al 28 Second, 4HNE-induced mitochondrial damage in the diabetic heart has been widely reported 25 ; however, only a few studies determined the role of 4HNE in other subcellular organelles like the proteasome in diabetic cardiomyopathy. 14,15 In the current study, we attempted to find whether 4HNE causes proteasome dysfunction in the diabetic heart of ISOinfused animals. We found increased 4HNE in the hearts of ISO-infused diabetic animals.…”

“…The ubiquitin-proteasome system becomes dysfunctional during long-term hyperglycaemia. 14,15 In earlier studies, we and others showed that cardiac 4HNE levels were increased in both type 1 and type 2 diabetes. [16][17][18][19] Therefore, we speculate that increased 4HNE protein adducts in streptozotocin (STZ)-injected hyperglycaemic rat hearts with isoproterenol (ISO) infusion may lead to proteasome dysfunction.…”

Diminution of hemoglobin-derived hemorphin: An underlying risk factor for cognitive deficit in diabetes

“…The chymotrypsin-like enzyme rather than trypsin-like protease contributes to the yield of hemorphins since their cleavage sites contained hydrophobic residues. The changes of proteasomal activity in alloxan-induced experimental model of diabetes are studied [11]. The results indicate a significantly decreased chymotrypsinlike activity, increased trypsin-like activity and unaltered peptidylglutamyl peptide-hydrolyzing activity.…”