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.
Previous studies have identified the mammalian homologue of Bv8 (mBv8), a small 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 cerebral cortex, limbic regions, cerebellar Purkinje cells, and dorsal and ventral 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 apoptotic death induced by switching the growing medium from 25 to 5 mM K+. Bv8 could 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 stimulated both the MAPK and the PI-3-K pathways, as revealed by Western blot analysis 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.
Melchiorri
D
D
Department of Human Physiology and Pharmacology, University of Rome La Sapienza, Piazzale Aldo Moro, 5, 00185 Rome, Italy. dmelchiorri@uniromal.it
Bruno
V
V
Besong
G
G
Ngomba
R T
RT
Cuomo
L
L
De Blasi
A
A
Copani
A
A
Moschella
C
C
Storto
M
M
Nicoletti
F
F
Lepperdinger
G
G
Passarelli
F
F
D029845:Amphibian Proteins; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002490:Central Nervous System / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D002525:Cerebellar Cortex / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides; D018696:Neuroprotective Agents / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D029845:Amphibian Proteins; C121344:Bv8 protein, Bombina variegata; D018690:Excitatory Amino Acid Agonists; D009479:Neuropeptides; D018696:Neuroprotective Agents; D011506:Proteins; D012333:RNA, Messenger; D016202:N-Methylaspartate; D019869:Phosphatidylinositol 3-Kinases