title: Hydrogen sulfide, endoplasmic reticulum stress and alcohol mediated neurotoxicity.
abstract: Alcohol is one of the most socially accepted addictive drugs in modern society. Its abuse affects virtually all organ systems with the central nervous system (CNS) being particularly vulnerable to excessive alcohol exposure. Alcohol exposure also causes profound damage to both the adult and developing brain. Excessive alcohol consumption induces numerous pathophysiological stress responses, one of which is the endoplasmic reticulum (ER) stress response. Potential mechanisms that trigger the alcohol induced ER stress response are either directly or indirectly related to alcohol metabolism, which include toxic levels of acetaldehyde and homocysteine, oxidative stress and abnormal epigenetic modifications. Growing evidence suggests that H2S is the most recently recognized gasotransmitter with tremendous physiological protective functions against oxidative stress induced neurotoxicity. In this review we address the alcohol induced oxidative stress mediated ER stress and the role of H2S in its mitigation in the context of alcohol neurotoxicity. Interruption of ER stress triggers is anticipated to have therapeutic benefits for alcohol mediated diseases and disorders.
authors.affiliation: Department of Physiology, School of Medicine, University of Louisville, Louisville, KY, 40202, USA.
authors.forename: Akash K
authors.initials: AK
authors.lastname: George
authors.affiliation: Department of Physiology, School of Medicine, University of Louisville, Louisville, KY, 40202, USA.
authors.forename: Jyotirmaya
authors.initials: J
authors.lastname: Behera
authors.affiliation: Department of Physiology, School of Medicine, University of Louisville, Louisville, KY, 40202, USA.
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Kelly
authors.affiliation: Department of Physiology, School of Medicine, University of Louisville, Louisville, KY, 40202, USA.
authors.forename: Yuankun
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: Department of Physiology, School of Medicine, University of Louisville, Louisville, KY, 40202, USA. Electronic address: n0tyag01@louisville.edu.
authors.forename: Neetu
authors.initials: N
authors.lastname: Tyagi
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D059865:Endoplasmic Reticulum Stress; D000431:Ethanol / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D015398:Signal Transduction
chemical_list: D017382:Reactive Oxygen Species; D000431:Ethanol; D006862:Hydrogen Sulfide
keywords: Alcohol; Endoplasmic reticulum stress; Homocysteine; Hydrogen sulfide; Reactive oxygen species; Unfolded protein response