Gender‐dimorphic regulation of DJ1 and its interactions with metabolic proteins in streptozotocin‐induced diabetic rats

Abstract

Regulation of DJ1 is associated with a number of human diseases. To determine the involvement of DJ1 in progression of diabetes in a genderdependent manner, we investigated its tissue-specific expression in streptozotocin (STZ)-induced diabetic male and female rats in this study. In animal experiments, females showed greater susceptibility towards developing diabetes because of lower insulin secretion and higher blood glucose levels as compared to male diabetic rats upon exposure to STZ. Immunoblotting confirmed sexually dimorphic regulation of DJ1 in various metabolic tissues such as the liver, pancreas and skeletal muscle. Immunofluorescence analysis revealed the location as well as reinforced the gender-dependent expression of DJ1 in hepatic tissue. Co-immunoprecipitation assay identified several interacting proteins with DJ1 whose functions were shown to be involved in various metabolic pathways viz. antioxidative and stress defence system, protein and methionine metabolism, nitrogen metabolism, urea metabolism, etc. Using GeneMANIA, a predictive web interface for gene functions, we showed for the first time that DJ1 may regulate T1DM via the JNK1 pathway, suggesting DJ1 interacts with other proteins from various metabolic pathways. We anticipate that the current data will provide insights into the aetiology of T1DM.

Differential proteomic profiling identifies novel molecular targets of pterostilbene against experimental diabetes

“…Hydroxymethylglutaryl‐CoA lyase is a mitochondrial enzyme that has an indispensable role in the formation of ketone bodies (acetoacetate), which are the precursors for glyoxylate intermediates such as methylglyoxal (MG) (Chaudhari, Kim, & Yun, ). We found a 76‐fold increase in the activity of this protein in the diabetic pancreas, which was suppressed by PTS treatment (0.05‐fold).…”

The role of DJ-1/Nrf2 pathway in the pathogenesis of diabetic nephropathy in rats

“…In fact, some studies have shown that with the ascending of blood glucose, the content of DJ-1 was increased to inhibit the expression of ROS. 27,28 . In addition, the renal protective effects in diabetic rats might be enhanced by the activation of Nrf2.…”

Sema4D Deficiency Enhances Glucose Tolerance Through Acceleration of GLUT2 Synthesis in Hepatocytes

“…Although hyperglycemia was less pronounced, diastolic dysfunction was more pronounced in STZ-induced diabetic female mice [52].Reduced circulating estradiol levels and imbalance in renal estrogen receptor expression accelerate the progression of diabetic nephropathy [53].Insulin sensitivity and susceptibility to diabetes are indeed associated with sex differences [54][55][56][57].However, it has also been reported that establishing equivalent diabetes in male and female Nos3-deficient mice results in a comparable onset of diabetic kidney injury [58].…”