ErbB-4 activation inhibits apoptosis in PC12 cells

Neuregulins. a large family of polypeptide growth factors, exert various di stinctive effects in the nervous system. neuregulins and their receptors ar e widely expressed in neurons implying important roles in neuronal cell fun ctions. Recently, we have shown that ErbB-4 receptors expressed in PC12 cel ls mediate neuregulin-induced differentiation. In the present study we demo nstrate that in the PC12-ErbB-4 cells, neuregulin rescues cells from apopto sis induced by serum deprivation or tumor necrosis factor (TNF)alpha treatm ent. The neuregulin-induced survival is comparable to the effect mediated b y the neurotrophic factor nerve growth factor (NGF). Both neuregulin and NG F protect cells from apoptosis induced by serum deprivation and TNF alpha t reatment. Moreover, neuregulin like NGF induces the survival of neuronal di fferentiated PC12-ErbB-4 cells. The survival effect of neuregulin is probab ly mediated by the phosphoinositide 3-kinase (PI3K) and protein kinase B/Ak t signaling pathways. Neuregulin induces the activation of PI3K and prolong ed activation of protein kinase B/Akt. In addition, inhibition of the PI3K activity prevented the neuregulin-induced survival effect. Taken together. these results indicate that survival induced by neuregulin in PC12-ErbB-4 cells requires PI3K signaling networks. (C) 2001 IBRO, Publi shed by Elsevier Science Ltd. All rights reserved.