Growth factor-mediated signal transduction and redox balance in isolated digestive gland cells from Mytilus galloprovincialis Lam.

In mammalian cells, a growing body of evidence indicates a relationship bet ween cellular redox balance and tyrosine kinase-mediated cell signalling. T he phosphorylative cascade activated by extracellular signals is inhibited by reducing conditions and stimulated by oxidative stress, in particular at the level of mitogen activated protein kinase (MAPK) activation. The musse l Mytilus typically shows variations in antioxidant defence systems and dec reases in glutathione content in response to both natural and contaminant e nvironmental stressors. In isolated mussel digestive gland cells, both epid ermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) have bee n recently demonstrated to activate tyrosine kinase receptors leading to mu ltiple responses; among these, stimulation of the key glycolytic enzymes ph osphofructokinase (PFK) and pyruvate kinase (PK). The present study investi gates the possible relationship between the tyrosine kinase-mediated metabo lic effects of growth factors and cellular redox balance in mussel cells. T he results demonstrate that the effects of growth factors on glycolytic enz ymes were abolished by cell pretreatment with the antioxidant N-acetyl-cyst eine (NAC). On the other hand, in cells where the glutathione content and s ynthesis were lowered either in vitro (by cell pretreatment with buthionine sulfoximine (BSO)); or in vivo (by mussel exposure to Cu2+) the metabolic effects of growth factors were unaffected. Moreover, the results show that, in both control and glutathione-depleted cells. growth factors can also re gulate the level of glutathione apparently by modulating, via phosphorylati ve mechanisms involving MAPK activation, the activity of gamma-glutamylcyst eine synthetase (GCS), the rate limiting enzyme in GSH biosynthesis. Overal l, this study extends the hypothesis that cell signalling is intimately rel ated to redox balance in marine invertebrate cells. (C) 2000 Elsevier Scien ce Inc. All rights reserved.