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Abstract: PO0707

The Potential Roles of NAD(P)H:Quinone Oxidoreductase 1 in the Development of Diabetic Nephropathy and Actin Polymerization

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Jeong, Jin young, Chungnam National University School of Medicine, Daejeon, Daejeon, Korea (the Republic of)
  • Choi, Dae Eun, Chungnam National University School of Medicine, Daejeon, Daejeon, Korea (the Republic of)
  • Chang, Yoon-Kyung, Daejeon Saint Mary's Hospital, Daejeon, Daejeon, Korea (the Republic of)
  • Na, Kiryang, Chungnam National University School of Medicine, Daejeon, Daejeon, Korea (the Republic of)
  • Lee, Kang Wook, Chungnam National University School of Medicine, Daejeon, Daejeon, Korea (the Republic of)
Background

Diabetic nephropathy (DN) is a major complication of diabetes mellitus. NAD(P)H:quinone oxidoreductase 1 (NQO1) is an antioxidant enzyme that has been involved in the progression of several kidney injuries. However, the roles of NQO1 in DN are still unclear. We investigated the effects of NQO1 deficiency in streptozotocin (STZ)-induced DN mice.

Methods

Wild-type (WT) and NQO1 KO male mice on C57BL/6N genetic background were used. For the diabetic nephropathy model, STZ was dissolved in citrate buffer (0.1 M; pH 4.5) and prepared immediately before use. Age-matched 8-week-old WT and NKO male mice were administered STZ (50 mg/kg body weight, intraperitoneal injection) after 4 h fasting, for five consecutive days. ACR were measued. Renal histology and molecular evaluation were done.

Results

NQO1 was upregulated in the glomerulus and podocytes under hyperglycemic conditions. NQO1 knockout (NKO) mice showed more severe changes in blood glucose and body weight than WT mice after STZ treatment. Furthermore, STZ-mediated pathological parameters including glomerular injury, blood urea nitrogen levels, and foot process width were more severe in NKO mice than WT mice. Importantly, urine albumin-to-creatinine ratio (ACR) was higher in healthy, non-treated NKO mice than WT mice. ACR response to STZ or LPS was dramatically increased in the urine of NKO mice compared to vehicle controls, while it maintained a normal range following treatment of WT mice. More importantly, we found that NQO1 can stimulate actin polymerization in an in vitro biochemical assay without directly the accumulation on F-actin.

Conclusion

NQO1 has an important role against the development of DN pathogenesis and is a novel contributor in actin reorganization via stimulating actin polymerization.