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Irreversible inactivation of magnesium‐dependent neutral sphingomyelinase 1 (NSM1) by peroxynitrite, a nitric oxide‐derived oxidant
Author(s) -
Josephs Michelle,
Katan Matilda,
Rodrigues-Lima Fernando
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03551-2
Subject(s) - peroxynitrite , chemistry , nitric oxide , hydrogen peroxide , sphingomyelin , glutathione , oxidative phosphorylation , magnesium , oxidative stress , thiol , biochemistry , enzyme , redox , biophysics , photochemistry , inorganic chemistry , superoxide , organic chemistry , membrane , biology
Previous results have indicated that the generation of ceramide by hydrolysis of sphingomyelin by magnesium‐dependent neutral sphingomyelinase 1 (NSM1) is reversibly inhibited by hydrogen peroxide (H 2 O 2 ) and oxidized glutathione (GSSG). This redox‐dependent reversible regulation of NSM1 activity has been shown to involve the reversible formation and breakage of disulfide bonds. In this paper, we show that peroxynitrite, a nitric oxide‐derived oxidant generated by SIN1, inactivates dose‐dependently the NSM1 activity in an irreversible manner. In addition, we show that, in contrast to the reversible inhibition of NSM1 by H 2 O 2 or GSSG which involves the formation of disulfide bonds, irreversible inactivation of this enzyme by peroxynitrite generated from SIN1 is likely due to definitive oxidative thiol modification. These results suggest that depending on the nature of the oxidative stress, the enzymatic activity of NSM1 could be reversibly or irreversibly inactivated.