The mammalian homologue of the novel peptide Bv8 is expressed in the central nervous system and supports neuronal survival by activating the MAP kinase/PI-3-kinase pathways
D. Melchiorri et al., The mammalian homologue of the novel peptide Bv8 is expressed in the central nervous system and supports neuronal survival by activating the MAP kinase/PI-3-kinase pathways, EUR J NEURO, 13(9), 2001, pp. 1694-1702
Previous studies have identified the mammalian homologue of Bv8 (mBv8), a s
mall protein originally isolated from skin secretions of the frog, Bombina
variegata. In situ hybridization showed that mBv8 RNA was widely expressed
in the rodent CNS, with high levels being detected in layer II of the cereb
ral cortex, limbic regions, cerebellar Purkinje cells, and dorsal and ventr
al horns of the spinal cord. A similar pattern of distribution was found by
examining the presence of mBv8 protein by immunocytochemistry. Addition of
frog Bv8 to cultured cerebellar granule cells reduced the extent of apopto
tic death induced by switching the growing medium from 25 to 5 mm K+. Bv8 c
ould also protect cultured cortical neurons against excitotoxic death. Both
effects were prevented by PD98059 and LY294002, which inhibit the mitogen-
activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI-3-K)
pathways, respectively. In cultured cerebellar granule cells, Bv8 stimulate
d both the MAPK and the PI-3-K pathways, as revealed by Western blot analys
is of phosphorylated p44/p42 MAPKs and phosphorylated Akt, respectively. We
conclude that mBv8 acts as an endogenous neurotrophic factor and supports
neuronal survival through the activation of the MAPK/PI-3-K pathways.