HSP72 Up-regulation with heat acclimation

In a companion paper in this journal, Amorim and coworkers reviewed recent human studies which show that Heat Shock Proteins (HSP72 and possibly HSP90) are elevated during heat acclimation. They suggest that these cellular changes result in both cellular and whole body thermotolerance. Thermotolerance after an initial sub-lethal heat exposure, has been shown repeatedly in cell studies, and has been linked with elevated intracellular HSP72 levels. Animal species that live in hot desert climates have been shown to have greater ability to synthesize HSPs. However, it is nearly impossible to prove if a similar induced heat tolerance occurs humans. Specifically, can previously heat exposed humans tolerate higher core body temperatures without ill effects? Amorim et al., suggest this may be the case and HSP72 upregulation may be the cause. Amorim and coworkers go further and suggest HSP72 is involved in inducing at least some of the classic signs of heat acclimation, such as increased sweating and skin blood flow and lower body temperatures. This suggestion is based on a study in which HSP up-regulation during heat acclimation was blocked by the ingestion of an HSP blocker, quercetin, and the thermoregulatory benefits also were blocked. A second human study also supports this idea. With a limited number of subjects, Kresfelder and coworkers identified a subset of heat intolerant individuals who possessed a modified allele of HSP72. The authors attributed the inability of these subjects to heat acclimate to their modified form of HSP72. Although Amorim and coworkers mostly limited their discussion to human studies, Tetievsky and coworkers studying rats have identified a variety of molecular pathways that are activated or deactivated during heat acclimation/de-acclimation/re-acclimation, including the HSP pathway. Heat exposures were found to turnon or turn-off specific genes and to induce epigenetic alterations that persist for long periods, resulting in a “molecular memory” which allows more rapid re-acclimation. Taylor, in a review of ethnic differences in heat tolerance suggests that such phenotypic changes (from molecular memory) after a single heat acclimation most likely are responsible for the improved heat tolerance previously attributed to ethnic differences in heat tolerance. From cell studies it is known that upon heat exposure, heat shock factor-1 (HSF-1) is released from the HSPHSF-1 complex. The HSF-1 trimerizes in the cytoplasm, becomes phosphorylated and then migrates into the nucleus where it binds with the heat shock element (HSE) in the promotors of the heat shock genes, stimulating translation and transcription of new HSP molecules. The freed and newly synthesized HSP have a multitude of beneficial effects, to both repair and minimize cellular damage (an initial response to short-term heat exposures), and later (with long-term heat acclimation) to up-regulate the cellular pathways to allow a more rapid synthesis of HSP72 and possibly interacting with other pathways (HIF, anti-oxidant, anti-inflammatory, anti-apoptosis) to develop thermotolerance against further environmental insult. Thus, a molecular response to heat acclimation, also seen in human leucocytes, is an intracellular accumulation of HSP72. Due to an increased HSP72 reserve after heat acclimation, there is less need to further augment HSP72 in response to an acute heat exposure.