Exogenous Hsc70, but not thermal preconditioning, confers protection to motoneurons subjected to oxidative stress.
Proper sensing of stress and the initiation of the stress response are critical to maintaining cell viability in response to noxious stimuli. Induction of the stress response prior to the exposure of a lethal stress (preconditioning) can be protective. Heat shock proteins (Hsps), the main products of the stress response, are considered to be responsible for this protective effect. Most cells readily initiate a stress response, but some neuronal phenotypes, including motoneurons (MNs), have a diminished capacity to do so. We have found that, given a proper stimulus, MNs can execute a heat stress response; but, it does not protect them from death caused by hydrogen peroxide (H(2)O(2)) induced oxidative stress, despite inhibiting H(2)O(2)-induced caspase activation. Conversely, we demonstrate that incubation with the heat shock cognate 70 (Hsc70) protein prior to oxidative insult can protect MNs from oxidative stress. This survival promoting effect may be mediated through the substrate binding domain (SBD) of Hsc70. Our data suggest that stress preconditioning may not be beneficial to MNs, but that pharmacological interventions and alternative means of acquiring components of the stress response are an effective means of ameliorating lethal stress in MNs and may be potentially useful therapeutically in preventing pathological MN loss.
Robinson
Mac B
MB
Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Taylor
Anna R
AR
Gifondorwa
David J
DJ
Tytell
Michael
M
Milligan
Carolanne E
CE
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D050883:HSC70 Heat-Shock Proteins / Q000737:chemistry / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000633:toxicity; D006979:Hyperthermia, Induced; D009046:Motor Neurons / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D017434:Protein Structure, Tertiary / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology; D013997:Time Factors
D004791:Enzyme Inhibitors; D050883:HSC70 Heat-Shock Proteins; D009842:Oligopeptides; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; D006861:Hydrogen Peroxide; D020169:Caspases; D002118:Calcium