Direct regulation of striated muscle myosins by nitric oxide and endogenous nitrosothiols

Alicia M. Evangelista, Vijay S. Rao, Ashley R. Filo, Nadzeya V. Marozkina, Allan Doctor, Dvid R. Jones, Benjamin Gaston, William H. Guilford

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Background: Nitric oxide (NO) has long been recognized to affect muscle contraction [1], both through activation of guanylyl cyclase and through modification of cysteines in proteins to yield S-nitrosothiols. While NO affects the contractile apparatus directly, the identities of the target myofibrillar proteins remain unknown. Here we report that nitrogen oxides directly regulate striated muscle myosins. Principal Findings: Exposure of skeletal and cardiac myosins to physiological concentrations of nitrogen oxides, including the endogenous nitrosothiol S-nitroso-L-cysteine, reduced the velocity of actin filaments over myosin in a dose-dependent and oxygen-dependent manner, caused a doubling of force as measured in a laser trap transducer, and caused Snitrosylation of cysteines in the myosin heavy chain. These biomechanical effects were not observed in response to Snitroso-D-cysteine, demonstrating specificity for the naturally occurring isomer. Both myosin heavy chain isoforms in rats and cardiac myosin heavy chain from human were S-nitrosylated in vivo. Significance: These data show that nitrosylation signaling acts as a molecular "gear shift" for myosin-an altogether novel mechanism by which striated muscle and cellular biomechanics may be regulated.

Original languageEnglish
Article numbere11209
JournalPloS one
Volume5
Issue number6
DOIs
StatePublished - Aug 11 2010

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    Evangelista, A. M., Rao, V. S., Filo, A. R., Marozkina, N. V., Doctor, A., Jones, D. R., Gaston, B., & Guilford, W. H. (2010). Direct regulation of striated muscle myosins by nitric oxide and endogenous nitrosothiols. PloS one, 5(6), [e11209]. https://doi.org/10.1371/journal.pone.0011209