Abstract: FR-PO1003
Ginseng Extract Reduces Tacrolimus-Induced Oxidative Stress by Modulating Autophagy in Pancreatic Beta Cell
Session Information
- Transplantation: Basic and Experimental
November 03, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Transplantation
- 1701 Transplantation: Basic and Experimental
Authors
- Lim, Sun Woo, The Catholic University of Korea, Seoul, Korea., Seoul, Korea (the Republic of)
- Shin, Yoo-Jin, The Catholic University of Korea, Seoul, Korea., Seoul, Korea (the Republic of)
- Luo, Kang, The Catholic University of Korea, Seoul, Korea., Seoul, Korea (the Republic of)
- Yang, Chul Woo, Seoul St. Mary's Hospital, Seoul, Korea (the Republic of)
Background
Growing evidence suggests that regulation of autophagy may be an effective approach to protect beta cells against various extra-/intracellular stimuli. We previously demonstrated that long-term treatment of calcineurin inhibitor causes excessive autophagosome burden and impaired autophagy clearance in pancreatic beta cells. This study investigated the effect of Korean red ginseng extract on autophagy modulation focused on oxidative stress.
Methods
The rat insulinoma cell line INS-1 was treated with Tac (40 ug/mL) and KRGE (100 pg/mL) with or without 3-methyladenine (3-MA, 10 mM) or bafilomycine A1 (BA, 2nM) for 6h. Mice were treated with Tac (1.5 mg/kg, subcutaneous) and KRGE (0.4 g/kg, orgal gavage) for 4 weeks. The effect of KRGE on Tac-induced diabetes was evaluated by assessing intraperitoneal glucose tolerance test, plasma insulin level, beta cell area, and 8-hydroxy-2'deoxyguanosin in serum and islet. Autophagy and mitochondria functions were examined by measuring either microtubule-associated protein 1 light chain 3 beta expression, the number of autophagic vacuoles, and lysosome function or oxygen consumption and mitochondrial membrane potential.
Results
In mice with Tac-induced diabetes mellitus, KRGE improved islet dysfunction, and decreased oxidative stress and autophagic vacuoles. In vitro study, KRGE decreased autophagosome formation and improved lysosomal degradation, accompanied by improved beta cell viability and insulin secretion. Addition 3-methyladenine (3-MA), an inhibitor of autophagosome, to KRGE further improved cell viability and insulin secretion, and bafilomycin A (BA), an inhibitor of lysosomal function, reduced those effects of KRGE. At subcellular level, Tac caused mitochondrial dysfunction (impaired mitochondrial oxygen consumption, ATP production, and increased reactive oxygen species production). But, KRGE improved these parameters. The effect of KRGE on the mitochondrial function enhanced by 3-MA but decreased by BA, suggesting causal relationship between KRGE effect and autophagy modulation in Tac-induced mitochondrial dysfunction.
Conclusion
These findings indicate that KRGE modulates autophagy favorably by reducing Tac-induced oxidative stress, and this effect is closely associated with improvement of mitochondrial function.