Kidney Res Clin Pract.  2019 Sep;38(3):318-325. 10.23876/j.krcp.18.0152.

Nrf2-Heme oxygenase-1 modulates autophagy and inhibits apoptosis triggered by elevated glucose levels in renal tubule cells

Affiliations
  • 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. starryroom@hanmail.net

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.
CONCLUSION
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.

Keyword

Autophagy; Diabetic nephropathies; Heme oxygenase-1; Nrf2; Sulforaphane

MeSH Terms

Apoptosis*
Autophagy*
Caspase 3
Diabetic Nephropathies
Down-Regulation
Glucose*
Heme Oxygenase-1
Homeostasis
Humans
Kidney
Lysosomes
NF-E2-Related Factor 2
Organelles
Oxidative Stress
Reactive Oxygen Species
Caspase 3
Glucose
Heme Oxygenase-1
NF-E2-Related Factor 2
Reactive Oxygen Species
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