Corticotropin-releasing factor is cytoprotective in Xenopus tadpole tail: coordination of ligand, receptor, and binding protein in tail muscle cell survival.
Upon metamorphosis, amphibian tadpoles lose their tails through programmed cell death induced by thyroid hormone (T3). Before transformation, the tail functions as an essential locomotory organ. The binding protein for the stress neuropeptide corticotropin-releasing factor (CRF; CRF-BP) is strongly up-regulated in the tail of Xenopus tadpoles during spontaneous or T3-induced metamorphosis. This finding led us to investigate physiological roles for CRF and CRF-BP in tadpole tail. We found CRF, CRF-BP, and functional CRF1 receptor in tail and CRF and functional CRF1 receptors, but not CRF-BP, in the tail muscle-derived cell line XLT-15. CRF, acting via the CRF1 receptor, slowed spontaneous tail regression in explant culture and caused a reduction in caspase 3/7 activity. CRF increased, but stable CRF-BP overexpression decreased, [3H]thymidine incorporation in XLT-15 cells. Overexpression of CRF-BP in vivo accelerated the loss of tail muscle cells during spontaneous metamorphosis. Lastly, exposure of tail explants to hypoxia increased CRF and urocortin 1 but strongly decreased CRF-BP mRNA expression. We show that CRF is expressed in tadpole tail, is up-regulated by environmental stressors, and is cytoprotective. The inhibitory binding protein for CRF is regulated by hormones or by environmental stressors and can modulate CRF bioactivity.
Boorse
Graham C
GC
Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, Michigan 48109-1048, USA.
Kholdani
Cyrus A
CA
Seasholtz
Audrey F
AF
Denver
Robert J
RJ
D000818:Animals; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism / Q000502:physiology*; D003432:Cross-Linking Reagents; D000242:Cyclic AMP / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D018274:Electroporation; D018014:Gene Transfer Techniques; D000860:Hypoxia; D007814:Larva; D008024:Ligands; D008675:Metamorphosis, Biological; D051379:Mice; D009132:Muscles / Q000378:metabolism; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013623:Tail; D015854:Up-Regulation; D054832:Urocortins; D014982:Xenopus laevis / Q000378:metabolism*; D000099052:CRF Receptor, Type 1
D003432:Cross-Linking Reagents; D017931:DNA Primers; D008024:Ligands; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D011994:Recombinant Proteins; D054832:Urocortins; D000099052:CRF Receptor, Type 1; D012313:RNA; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP; C505409:Casp3 protein, mouse; C505524:Casp7 protein, mouse; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases