RRC ID 30634
Author Kourtis N, Nikoletopoulou V, Tavernarakis N.
Title Small heat-shock proteins protect from heat-stroke-associated neurodegeneration.
Journal Nature
Abstract Heat stroke is a life-threatening condition, characterized by catastrophic collapse of thermoregulation and extreme hyperthermia. In recent years, intensification of heat waves has caused a surge of heat-stroke fatalities. The mechanisms underlying heat-related pathology are poorly understood. Here we show that heat stroke triggers pervasive necrotic cell death and neurodegeneration in Caenorhabditis elegans. Preconditioning of animals at a mildly elevated temperature strongly protects from heat-induced necrosis. The heat-shock transcription factor HSF-1 and the small heat-shock protein HSP-16.1 mediate cytoprotection by preconditioning. HSP-16.1 localizes to the Golgi, where it functions with the Ca(2+)- and Mn(2+)-transporting ATPase PMR-1 to maintain Ca(2+) homeostasis under heat stroke. Preconditioning also suppresses cell death inflicted by diverse insults, and protects mammalian neurons from heat cytotoxicity. These findings reveal an evolutionarily conserved mechanism that defends against diverse necrotic stimuli, and may be relevant to heat stroke and other pathological conditions involving necrosis in humans.
Volume 490(7419)
Pages 213-8
Published 2012-10-11
DOI 10.1038/nature11417
PII nature11417
PMID 22972192
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Calcium / metabolism Calcium-Transporting ATPases / genetics Calcium-Transporting ATPases / metabolism Cells, Cultured Cytoplasm / metabolism Heat-Shock Proteins, Small / metabolism* Heat-Shock Response / physiology* Hot Temperature Larva Mice Mutation Necrosis / etiology Necrosis / physiopathology Neurons / pathology* Survival Analysis
IF 43.07
Times Cited 50
C.elegans tm515 tm1840 tm690 tm1750 tm1093 tm2318