Heat Acclimation-Mediated Cross-Tolerance: Origins in within-Life Epigenetics?

Michal Horowitz

doi:10.3389/fphys.2017.00548

Abstract

The primary outcome of heat acclimation is increased thermotolerance, which stems from enhancement of innate cytoprotective pathways. These pathways produce “ON CALL” molecules that can combat stressors to which the body has never been exposed, via cross-tolerance mechanisms (heat acclimation-mediated cross-tolerance—HACT). The foundation of HACT lies in the sharing of generic stress signaling, combined with tissue/organ- specific protective responses. HACT becomes apparent when acclimatory homeostasis is achieved, lasts for several weeks, and has a memory. HACT differs from other forms of temporal protective mechanisms activated by exposure to lower “doses” of the stressor, which induce adaptation to higher “doses” of the same/different stressor; e.g., preconditioning, hormesis. These terms have been adopted by biochemists, toxicologists, and physiologists to describe the rapid cellular strategies ensuring homeostasis. HACT employs two major protective avenues: constitutive injury attenuation and abrupt post-insult release of help signals enhanced by acclimation. To date, the injury-attenuating features seen in all organs studied include fast-responding, enlarged cytoprotective reserves with HSPs, anti-oxidative, anti-apoptotic molecules, and HIF-1α nuclear and mitochondrial target gene products. Using cardiac ischemia and brain hypoxia models as a guide to the broader framework of phenotypic plasticity, HACT is enabled by a metabolic shift induced by HIF-1α and there are less injuries caused by Ca+2 overload, via channel or complex-protein remodeling, or decreased channel abundance. Epigenetic markers such as post-translational histone modification and altered levels of chromatin modifiers during acclimation and its decline suggest that dynamic epigenetic mechanisms controlling gene expression induce HACT and acclimation memory, to enable the rapid return of the protected phenotype. In this review the link between in vivo physiological evidence and the associated cellular and molecular mechanisms leading to HACT and its difference from short-acting cross-tolerance strategies will be discussed.

Highlights

Research into the important topic of acclimation/acclimatization to an adverse environment began in the late Nineteenth century, in the wake of colonialization, and the necessity to adapt to harsh occupational environments in hot tropical countries
We are referring to decreased Ca2+ sensitivity seen in both the heat acclimation (HA) and heat acclimation combined with exercise training (HAEX), but not in the exercise training (EX) groups (Figure 2B; Cohen et al, 2007; Kodesh et al, 2011). These findings suggest that the consequences of prolonged heat exposure predominate in this case, at least
We have shown that a continuous hypoxia inducible transcription factor 1α (HIF-1α) dimerization blockade is needed to attenuate heat acclimation mediated crosstolerance (HACT), even though no changes in acclimatory levels of HSP72 were measured (Alexander-Shani et al, 2017). his attenuation adds metabolic aspects to HACT

Summary

Introduction

Research into the important topic of acclimation/acclimatization to an adverse environment began in the late Nineteenth century, in the wake of colonialization, and the necessity to adapt to harsh occupational environments in hot tropical countries. To date, accumulating experimental evidence and bioinformatic analyses of the HA transcriptome have established that, irrespective of the organ studied, HACT employs a two-tier protective response: (i) constitutive injury attenuation; and (ii) the abrupt, post-insult release of help signals that are enhanced in the acclimated phenotype.

Results

Conclusion