Heat shock protein 72 overexpression protects against hyperthermia, circulatory shock, and cerebral ischemia during heatstroke.
This study extends our earlier studies in rats by applying our heatstroke model to a new species. Additionally, transgenic mice are used to examine the role of heat shock protein (HSP) 72 in experimental heatstroke. Transgenic mice that were heterozygous for a porcine HSP70i gene ([+]HSP72), transgene-negative littermate controls ([-]HSP72), and normal Institute of Cancer Research strain mice (ICR) under pentobarbital sodium anesthesia were subjected to heat stress (40 degrees C) to induce heatstroke. In [-]HSP72 or ICR, the values for mean arterial pressure, the striatal blood flow, and the striatal PO2 after the onset of heatstroke were significantly lower than those in preheat controls. The core and brain temperatures, the extracellular concentrations of ischemic and injury markers in the striatum, and the striatal neuronal damage scores were significantly greater than those in the preheat controls. In [-]HSP72 or ICR, the body temperatures, cell ischemia content, and injury marker in the striatum were significantly higher, and the mean arterial pressure, striatal blood flow, and striatal PO2 concentration were significantly lower during heatstroke than in [+]HSP72. Accordingly, the latency and the survival times for [+]HSP72 significantly exceeded those of [-]HSP72 or ICR. These results demonstrate that the overexpression of HSP72 in multiple organs improves survival during heatstroke by reducing hyperthermia, circulatory shock, and cerebral ischemia and damage in mice.
Lee
W C
WC
Division of Biotechnology, Animal Technology Institute Taiwan, Miaoli, Taiwan.
Wen
H C
HC
Chang
C P
CP
Chen
M Y
MY
Lin
M T
MT
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001833:Body Temperature Regulation / Q000235:genetics / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000503:physiopathology; D002545:Brain Ischemia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D002874:Chromosome Mapping; D005334:Fever / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D005786:Gene Expression Regulation / Q000502:physiology*; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism*; D018882:Heat Stress Disorders / Q000503:physiopathology; D018883:Heat Stroke / Q000150:complications / Q000503:physiopathology*; D006973:Hypertension / Q000503:physiopathology / Q000517:prevention & control; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D012039:Regional Blood Flow / Q000502:physiology; D012769:Shock / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D013552:Swine; D019076:Transgenes / Q000235:genetics
D050884:HSP72 Heat-Shock Proteins