Identification of global transcriptional variations in human peripheral blood mononuclear cells two months postheat injury helps categorization heat-tolerant or heat-intolerant phenotypes

Michal Horowitz*, Dani Kopeliovich, Reouven Berdugo, Yoav Smith, Sharona Elgavish, Haggai Schermann, Dani S. Moran

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Thermal intolerance may limit activity in hostile environments. After heat illness, two physiologically distinct phenotypes evolve: heat tolerant (HT) and heat intolerant (HI). The recognition that heat illness alters gene expression justified revisiting the established physiological concept of HI. We used a DNA microarray to examine the global transcriptional response in peripheral blood mononuclear cells (PMBCs) from HI and HT phenotypes, categorized 2-mo postheat injury using a functional physiological heat-tolerance test (HTT, 40C)-Recovery (R, 24C) protocol. The impact of recurrent heat stress was studied in vitro using peripheral blood mononuclear cells (PBMCs) from controls (participants with no history of heat injury), HI, and HT (categorized by functional HTT) with a customized NanoString array. There were significant differences under basal conditions between the HI and HT. HI were more immunological alerted. Almost no shared genes were found between end-HTT and recovery phases, suggesting vast cellular plasticity. In HI, mitochondrial function was dysregulated, canonical pathways associated with exercise endurance-NRF2 and insulin were downregulated, whereas AMPK and peroxisome proliferator-activated receptor (PPAR) were upregulated. HT exhibited reciprocal responses, suggesting that energy dysregulation found in HI interfered with performance in the heat. The endoplasmic-reticulum stress response was also suppressed in HI. In vitro HTT (43C) abolished differences between HI and HT PBMCs including the HSPs genes, whereas controls showed profound HSPs upregulation.

Original languageAmerican English
Pages (from-to)R691-R707
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume324
Issue number6
DOIs
StatePublished - 1 Jun 2023

Bibliographical note

Publisher Copyright:
Copyright © 2023 the American Physiological Society.

Keywords

  • Canonical pathways
  • Enriched functions annotation
  • Heat intolerance
  • Heat tolerance test
  • In vitro recurrent heat tolerance test

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