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Possible role for nitric oxide dysregulation in critical illness myopathy
Author(s) -
Capasso Margherita,
Muzio Antonio Di,
Pandolfi Assunta,
Pace Marta,
Tomo Pamela Di,
Ragno Michele,
Uncini Antonino
Publication year - 2008
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.20907
Subject(s) - peroxynitrite , nitric oxide , nitrotyrosine , nos1 , myopathy , downregulation and upregulation , muscle biopsy , medicine , endocrinology , western blot , sarcolemma , nitric oxide synthase , chemistry , biology , myocyte , biochemistry , biopsy , superoxide , enzyme , gene
Muscle fiber inexcitability and myosin loss underlie weakness in critical illness myopathy (CIM). Nitric oxide (NO) takes part in the maintenance of muscle fiber resting potential and, in pathological conditions accompanied by oxidative stress, may damage proteins through peroxynitrite generation. Sepsis and other conditions associated with CIM may differentially affect expression of NO synthases (NOSs), so that both downregulation and upregulation with excessive peroxynitrite production can be hypothesized. In six patients with CIM we studied NOS1, NOS2, and NOS3 protein expression by immunohistochemistry and Western blot. To investigate peroxynitrite production, we performed immunohistochemistry for nitrotyrosine and measured nitrotyrosine levels by enzyme‐linked immunosorbent assay. In three patients, sarcolemmal staining for NOS1 was selectively absent. In the others, it was absent in atrophic fibers and absent or reduced in non‐atrophic fibers. Total NOS1 protein content was reduced by 41% in patients compared to controls, whereas no significant changes were found in levels and localization of NOS2, NOS3, and nitrotyrosine. Further studies are warranted to determine whether NOS1 loss plays a role in the pathophysiology of CIM, possibly reducing the release of NO at the sarcolemma and affecting muscle fiber excitability. Muscle Nerve, 2007