Nrf2-Heme oxygenase-1 modulates autophagy and inhibits apoptosis triggered by elevated glucose levels in renal tubule cells
Joo-Heon Kim1 , Kyeong Min Kim2 , Jin Uk Jeong2 , Jong Ho Shin2 , Jae Min Shin1 , Ki Tae Bang2
1Department of Pathology, Eulji University Hospital, Eulji University College of Medicine, Daejeon, Korea
2Division of Nephrology, Department of Internal Medicine, Eulji University Hospital, Eulji University College of Medicine, Daejeon, Korea
Correspondence to: Ki Tae Bang
Division of Nephrology, Department of Internal Medicine, Eulji University Hospital, Eulji University College of Medicine, 95 Dunsanseo-ro, Seo-gu, Daejeon 35233, Korea. E-mail: starryroom@ hanmail.net
Received: December 10, 2018; Revised: March 27, 2019; Accepted: March 28, 2019; Published online: May 8, 2019.
© The Korean Society of Nephrology. All rights reserved.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons. org/licenses/by-nc-nd/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract

Background: Autophagy is a highly balanced process in which lysosomes remove aged and damaged organelles and cellular proteins. Autophagy is essential to maintain homeostasis in the kidneys.

Methods: Using human renal tubule cells HK-2, we assessed the impact of high glucose (HG) on autophagy. We also evaluated the capability of sulforaphane (SFN) to protect the HK-2 cells from HG-induced apoptosis by modulating autophagy.

Results: SFN modulated autophagy and decreased apoptosis in the HK-2 cells that were cultured in 250 mM glucose medium for two days. The reactive oxygen species (ROS) levels increased, as expected, in the cells cultured in the 250 mM glucose medium. However, the SFN decreased the ROS levels in the HK-2 cells. The overexpression of heme oxygenase-1 (HO-1) by SFN decreased the expression of LC3 and beclin-1. LC3 and beclin-1 were involved in the downregulation of caspase-3 that was observed in the HG-induced cells.

Conclusions: The activation of nuclear factor E2-related factor 2 (Nrf2)-HO-1 inhibited ROS expression and subsequently attenuated autophagy and cell apoptosis after HG injury was decreased. HG injury led to the activation of autophagy and HO-1 in order to combat oxidative stress and protect against cell apoptosis. Therefore, HO-1 activation can prevent ROS development and oxidative stress during HG injury, which considerably decreases autophagy and apoptosis.

Keywords: Autophagy, Diabetic nephropathies, Heme oxygenase-1, Nrf2, Sulforaphane


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