Critical roles of Rho-associated kinase in membrane blebbing and mitochondrial pathway of apoptosis caused by 1-butanol

Toxicology in Vitro : an International Journal Published in Association with BIBRA
Kanako NoritakeKoichi Uemura

Abstract

Alcohols are widely used as industrial solvents and chemical intermediates but can cause serious damage to human health. Nevertheless, few studies have addressed the molecular mechanisms underlying the cytotoxicity of industrial alcohols, with the notable exception of ethanol. The goal of our current study is to elucidate the molecular mechanism of cytotoxicity caused by primary alcohols containing longer carbon chains than ethanol. We find that 1-butanol induces morphological changes in H9c2 cardiomyoblastoma including nuclear condensation and membrane blebbing, both of which are features of apoptotic response. Moreover, a decrease in the mitochondrial membrane potential, the cytosolic release of cytochrome c, and the activation of caspase 9 and 3 was observed, thus revealing the activation of the mitochondrial apoptotic pathway by 1-butanol. The addition of Y-27632, a specific inhibitor of Rho-associated kinase (ROCK), suppressed the membrane blebbing and mitochondrial apoptotic pathway. In comparison z-VAD-fmk, a pan-caspase inhibitor, did not inhibit membrane blebbing but did prevent cell death following exposure to 1-butanol. These results indicate that mitochondrial pathway of apoptosis and membrane blebbing are parallel ...Continue Reading

References

Jan 1, 1969·Annual Review of Pharmacology·R B Forney, R N Harger
Mar 1, 1997·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·S C McKarnsD J Doolittle
Mar 14, 1998·The Journal of Cell Biology·J C MillsR N Pittman
Jun 15, 1999·Toxicological Sciences : an Official Journal of the Society of Toxicology·O StrubeltM Younes
Mar 29, 2000·The Journal of Biological Chemistry·M C SubausteK M Hahn
Jun 5, 2003·Nature Reviews. Molecular Cell Biology·Kirsi Riento, Anne J Ridley
Nov 20, 2004·Journal of Cardiovascular Pharmacology·Zhanjun GuanJoseph J Bahl
May 18, 2005·Alcoholism, Clinical and Experimental Research·György HajnóczkyEmanuel Rubin
May 20, 2005·Nature·Guillaume T CharrasT J Mitchison
Dec 14, 2005·Alcoholism, Clinical and Experimental Research·Tomás Zima, Marta Kalousová
Jan 5, 2006·Journal of Cell Science·Rebeca MiñambresConsuelo Guerri
Sep 20, 2006·Proceedings of the National Academy of Sciences of the United States of America·Jiang ChangRobert J Schwartz
Jan 20, 2007·The Journal of Biological Chemistry·Dominic P Del ReJoan Heller Brown
Oct 9, 2007·Biophysical Journal·Guillaume T CharrasL Mahadevan
Jul 17, 2008·Nature Reviews. Molecular Cell Biology·Guillaume Charras, Ewa Paluch
Oct 11, 2008·Cell Death and Differentiation·G KroemerUNKNOWN Nomenclature Committee on Cell Death 2009
Dec 2, 2008·Toxicology·Nathalie Zucchini-PascalRoger Rahmani
Oct 23, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jean-Yves TinevezEwa Paluch
Sep 28, 2010·Biological Chemistry·Juliane I Beier, Craig J McClain

❮ Previous
Next ❯

Citations

Mar 28, 2013·Cardiovascular Toxicology·Marie BesshoKoichi Uemura
Nov 1, 2015·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Tsutomu MaedaYoshitaka Matsusue
Oct 13, 2018·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Andrew S GoldsteinMark A Greiner
Mar 10, 2017·Journal of Biomaterials Science. Polymer Edition·Qin ZouYubao Li
Sep 15, 2017·The Journal of Toxicological Sciences·Kanako NoritakeKoichi Uemura

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis