Bcl-xL and caspase inhibition increase the survival of rat oxytocin and vasopressin magnocellular neurons in organotypic culture.
Hypothalamic magnocellular neurons (MCNs) are highly vulnerable to axotomy-induced cell death in vivo and in vitro. In this study, we determined whether the anti-apoptotic agent Bcl-xL, a member of the Bcl-2 family which prevents programmed cell death in the central nervous system, can rescue oxytocin (OT) and vasopressin (VP) MCNs in the supraoptic nucleus (SON) in organotypic culture. We found that the novel, membrane permeant form of Bcl-xL that we employed in these studies protected both OT and VP MCNs from degeneration as long as the Bcl-xL was present in the medium. In contrast, z-VAD-fmk, an inhibitor of caspases that are involved in apoptosis, was less effective in that it significantly rescued OT MCNs (P < 0.01) but not VP MCNs (P > 0.09). Unlike the Bcl-xL, Z-VAD-fmk's effectiveness in reducing MCN cell death was not sustained for the full 15 days in vitro.
House
Shirley B
SB
Laboratory of Neurochemistry, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Rusnak
Milan
M
Liu
Xiu-Huai
XH
Youle
Richard J
RJ
Gainer
Harold
H
D000818:Animals; D061945:Caspase Inhibitors; D020169:Caspases / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D010121:Oxytocin / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014667:Vasopressins / Q000502:physiology*; D051020:bcl-X Protein / Q000037:antagonists & inhibitors* / Q000502:physiology
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D051020:bcl-X Protein; D014667:Vasopressins; D010121:Oxytocin; D020169:Caspases