Acute ethanol induces apoptosis by stimulating TRPC6 via elevation of superoxide in oxygenated podocytes

• Type of Material: Article
• Authors: Xiao-Yu Lu, Harbin Medical University; Bing-Chen Liu, Emory University; Li-Hua Wang, Harbin Medical University; Li-Li Yang, Emory University; Qing Bao, Emory University; Yujia Zhai, Emory University; Abdel Alli, Emory University; Tiffany Thai, Emory University; Douglas C Eaton, Emory University; Wei-Zhi Wang, Harbin Medical University; He-Ping Ma, Emory University
• Language: English
• Date: 2015-05-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Elsevier B.V.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bbamcr.2015.01.007
• Title of Journal or Parent Work: Biochimica et Biophysica Acta Molecular and Cell Biology of Lipids
• ISSN: 1388-1981
• Volume: 1853
• Issue: 5
• Start Page: 965
• End Page: 974
• Grant/Funding Information: This research was supported by the Department of Health and Human Services (National Institutes of Health Grants 5R01-DK067110 and R01-DK100582 to He-Ping Ma), the Heilongjiang Province Postdoctoral Foundation (LBH-Z13162 to Bing-Chen Liu), and the National Natural Science Foundation of China (Projects 81171122 and 81371324 to Li-Hua Wang).
• Keywords: Science & Technology; KIDNEY; Cell Biology; Patch-clamp technique; Oxidative stress; LUNG INJURY; Catalase; Intracellular Ca2+; INGESTION; Life Sciences & Biomedicine; Biochemistry & Molecular Biology; DYSFUNCTION; ISCHEMIA-REPERFUSION; NOX2; RATS; OXIDATIVE STRESS; CHANNEL; Confocal microscopy; HYDROGEN-PEROXIDE; ISCHEMIA/REPERFUSION INJURY
• Research Categories: Biology, Physiology; Chemistry, Biochemistry

Abstract

Our recent studies indicate that hydrogen peroxide (H 2 O 2 ) only at high concentrations can cause oxidative stress in renal epithelial cells and induce apoptosis of podocytes. Consistently, the present study shows that H 2 O 2 , even at 1mM, failed to induce intracellular oxidative stress and apoptosis of the podocytes due to efficient activity of catalase, an enzyme which degrades H 2 O 2 to produce water and oxygen (O 2 ). However, H 2 O 2 acted as a source of O 2 to allow acute ethanol to induce superoxide production and cause apoptosis of the podocytes. In contrast, acute ethanol alone did not elevate intracellular superoxide, even though it stimulates expression and translocation of p47phox to the plasma membrane. Inhibition of catalase abolished not only O 2 production from H 2 O 2 degradation, but also NOX2-dependent superoxide production in the podocytes challenged by both H 2 O 2 and acute ethanol. In parallel, acute ethanol in the presence of H 2 O 2 , but neither ethanol nor H 2 O 2 alone, stimulated transient receptor potential canonical 6 (TRPC6) channels and caused TRPC6-dependent elevation of intracellular Ca 2+ . These data suggest that exogenous H 2 O 2 does not induce oxidative stress due to rapid degradation to produce O 2 in the podocytes, but the oxygenated podocytes become sensitive to acute ethanol challenge and undergo apoptosis via a TRPC6-dependent elevation of intracellular Ca 2+ . Since cultured podocytes are considered in hypoxic conditions, H 2 O 2 may be used as a source of O 2 to establish an ischemia-reperfusion model in some type of cultured cells in which H 2 O 2 does not directly induce intracellular oxidative stress.