Hydrogen sulfide donor NaHS induces death of alveolar epithelial L2 cells that is associated with cellular shrinkage, transgelin expression and myosin phosphorylation.
Hydrogen sulfide (H2S) is a highly toxic gaseous molecule that causes death to humans exposed to high concentrations. H2S is absorbed into the body through the alveolar epithelium and other tissues. The aim of this study is to evaluate the molecular mechanism underling acute lung injury caused by the inhalation of high concentrations of H2S. Rat lung epithelium-derived L2 cells were exposed to a H2S donor, NaHS, at concentrations of 2-4 mM for 1-6 hr. NaHS caused shrinkage and death of the cells without caspase activation. An actin-binding protein, transgelin, was identified as one of the NaHS-inducible proteins in the cells. NaHS increased myosin light chain (MLC) phosphorylation, indicating that actomyosin-mediated cellular contractility and/or motility could be increased after NaHS exposure. The administration of ML-7, a myosin light chain kinase (MLCK) inhibitor, accelerated cell death after NaHS exposure. Based on these data, we conclude that the increase in MLC phosphorylation in response to NaHS exposure is a cellular protective reaction against NaHS toxicity. Enhancements in smooth muscle cell properties such as transgelin expression and actomyosin-mediated contractility/motility might be involved in cell survival after NaHS exposure.
Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University.
Yusuke
Y
Fujii
Takeshi
T
Funakoshi
Kana
K
Unuma
Kanako
K
Noritake
Toshihiko
T
Aki
Koichi
K
Uemura
D055371:Acute Lung Injury / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D048429:Cell Size / Q000187:drug effects*; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000633:toxicity*; D008840:Microfilament Proteins / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism*; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D010766:Phosphorylation; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013440:Sulfides / Q000378:metabolism / Q000633:toxicity*; D013997:Time Factors
D008840:Microfilament Proteins; D009124:Muscle Proteins; D018994:Myosin Light Chains; D013440:Sulfides; C051615:transgelin; D009219:Myosin-Light-Chain Kinase; C025451:sodium bisulfide; D006862:Hydrogen Sulfide