Induction of neuronal apoptosis by Semaphorin3A-derived peptide.
Collapsin-1/Semaphorin3A (Sema3A) belongs to the secreted type III semaphorins family of axon guidance molecules with chemorepulsive activity, and is suggested to play a major role in navigating axonal networks throughout development into their correct destinations. We have previously shown that semaphorins are mediators of neuronal apoptosis and can induce neuronal death in the absence of any other apoptotic trigger. We report here that exposure of neuronal cells to a small conserved peptide derived from Sema3A initiates an apoptotic death process. Administration of this peptide to cultured chick sympathetic and mouse cerebellar granule neurons caused a marked shrinkage of their axonal network and cell death, which was characterized as apoptotic, based on nuclear staining. Attenuation of neuronal cell death was obtained by treatment with antioxidants and by vascular endothelial growth factor. Survival of neurons exposed to this peptide increased by co-treatment with caspase inhibitors. Induction of apoptosis was specific to neuronal cells, similarly to that induced by the full-length Sema3A protein. Our findings therefore suggest active participation of this conserved Sema3A-derived peptide in semaphorin-induced neuronal death process.
Shirvan
A
A
Department of Neurology and Felsenstein Medical Research Center, Rabin Medical Center, Beilinson Campus and the Sackler School of Medicine, 49100, Petach Tiqva, Israel. anat@nst.co,il
Shina
R
R
Ziv
I
I
Melamed
E
E
Barzilai
A
A
D000111:Acetylcysteine / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001369:Axons / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002531:Cerebellum / Q000166:cytology*; D002540:Cerebral Cortex / Q000166:cytology; D002642:Chick Embryo; D004229:Dithiothreitol / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005728:Ganglia, Sympathetic / Q000166:cytology*; D020287:In Situ Nick-End Labeling; D008222:Lymphokines / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000975:Antioxidants; D016228:Endothelial Growth Factors; D016166:Free Radical Scavengers; D008222:Lymphokines; D010446:Peptide Fragments; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D004229:Dithiothreitol; D004298:Dopamine; D000111:Acetylcysteine