Heat shock protein 72 overexpression protects against hyperthermia, circulatory shock, and cerebral ischemia during heatstroke

Abstract

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.

Effects of heat stress on serum insulin, adipokines, AMP-activated protein kinase, and heat shock signal molecules in dairy cows

“…Transcriptionally active HSF increases the expression of HSPs that promote the refolding of misfolded proteins (Li et al, 2011). Overexpression of HSPs protects against hyperthermia during heat stress (Lee et al, 2006). The rise in the concentration of HSF and HSPs could serve as a rapid protective mechanism against heat stress to maintain the homeostasis.…”

Metabolic and hormonal acclimation to heat stress in domesticated ruminants

“…To accomplish this at the genomic level, the genes associated with acclimation, adaptation and thermotolerance need to be identified and studied. The central role that Hsp have in cytoprotection during heat stress is shown by the fact that Hsp overexpression protects against hyperthermia and cerebral ischemia during the heat stroke (Lee et al, 2006). Heat shock (418C) causes increased Hsp synthesis, decreased protein synthesis, mitochondrial swelling and movement of organelles away from the plasma membrane associated with cytoskeletal reorganization (Edwards and Hansen, 1996;Edwards et al, 1997;Rivera et al, 2003).…”

Characterization of genes and pathways that respond to heat stress in Holstein calves through transcriptome analysis

“…Early studies had revealed that a genetic network of heat shock transcription factors is responsible for various responses to HS (Pirkkala et al 2001;Page et al 2006). In addition, the central role of heat shock proteins (HSPs) has been described as protecting hyperthermia, circulatory shock, and cerebral ischemia during heat stroke (Lee et al 2006). Gene expression profiling of blood provides an opportunity to clarify the response of the animal to heat stress on a global level, and moreover, it will result in identification of target genes that accurately reflects not only the physiological state of the animal but also the response of the animal through the activation of various cellular processes involving various cell types.…”