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Mechanical stimulation of skeletal muscle increases prostaglandin F 2α production, cyclooxygenase activity, and cell growth by a pertussis toxin sensitive mechanism
Author(s) -
Vandenburgh Herman H.,
Shansky Janet,
Solerssi Rosa,
Chromiak Joseph
Publication year - 1995
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041630209
Subject(s) - pertussis toxin , cyclooxygenase , prostaglandin e2 , stimulation , medicine , skeletal muscle , prostaglandin , endocrinology , prostaglandin e , cell growth , myocyte , chemistry , biology , enzyme , biochemistry , signal transduction , g protein
Repetitive mechanical stimulation of differentiated skeletal muscle in tissue culture increased the long‐term production of prostaglandin F 2α , an anabolic stimulator of myofiber growth. Within 4 h of initiating mechanical stimulation, the enzymatic activity of cyclooxygenase (prostaglandin GH synthase [PGHS]), a regulatory enzyme in prostaglandin synthesis, was increased 82% ( P <.005), and this increase was maintained for at least 24 h. Kinetic analysis of stretch‐activated cyclooxygenase activity indicated a two to threefold decrease in the enzyme's K m , with little change in its V max . Immunocytochemical analysis of the cell cultures indicated the presence of high levels of the mitogen‐inducible isoform of cyclooxygenase (PGHS‐2) in the skeletal myofibers compared to the interstitial fibroblasts. While the stretch‐induced increase in cyclooxygenase enzymatic activity was not inhibited by tetrodotoxin and therefore was independent of cellular electrical activity, the G protein inhibitor pertussis toxin prevented stretch‐induced cyclooxygenase activation. Pertussis toxin also inhibited stretch‐induced increases in PGF 2α production, phospholipase D activation, and cell growth. It is concluded that stretch of skeletal muscle increases muscle cell growth through a G protein‐dependent process involving the activation of cyclooxygenase, an immediate early gene product. © 1995 Wiley‐Liss, Inc.