Hypoglycemia Impairs the Heat Shock Protein Response: A Risk for Heat Shock in Cattle?

Samuel A Atkin,Stephen L Atkin,Alexandra E Butler,Abu Saleh Md Moin

doi:10.3389/fvets.2022.822310

Abstract

BackgroundHeat stress (HS) in cattle is a major debilitating problem, affecting health and milk yield. Physiologically, HS has been shown to lower blood glucose levels to 2.5 mmol/l (45 mg/dl) and results in upregulation of heat shock proteins (HSPs), eliciting the heat shock response (HSR) of which HSP90, 70 and 27 have been shown to be protective. However, it is unclear if the HSP response is blunted by decreased glucose, thereby preventing adaptive mechanisms. To address this question, this exploratory reverse translational study on the effects of hypoglycemia on the HSP pathway was undertaken.MethodsA human prospective, study in healthy control individuals (n = 23) was undertaken. Subjects underwent hyperinsulinemic-induced hypoglycemia [≤2.0 mmol/L (36 mg/dl)] with blood sampling at baseline, at hypoglycemia and for a 24-h post-hypoglycemia follow-up period. Proteomic analysis of the heat shock-related protein pathway, the pathway associated with HS in cattle, was performed.ResultsIn response to hypoglycemia, HS pathway proteins were significantly decreased (p < 0.05): HSP70 and HSP27 (at hypoglycemia); DnaJ homolog subfamily B member 1 (DNAJB1), Stress-induced-phosphoprotein 1 (STIP1) and the ubiquitin pathway proteins, Ubiquitin-conjugating enzyme (UBE2L3) and Ubiquitin-conjugating enzyme E2 N (UBE2N) (at 30-min post-hypoglycemia); HSP90 (at 2-h post-hypoglycemia). STIP1, UBE2L3, and UBE2N remained suppressed at 24-h.ConclusionHeat stress in cattle reduces blood glucose that, in turn, may blunt the HS pathway protective response, including HSP 90, 70, 27 and the ubiquitin proteins, leading to adverse outcomes. Monitoring of blood glucose in susceptible cattle may allow for earlier intervention and may also identify those animals at greatest risk to ensure that milk yield is not compromised.

Highlights

Climate change represents a global threat, with [1] increasing temperatures and frequent extreme weather events directly affecting humans
heat shock protein 70 (HSP70) was significantly decreased (p < 0.05) and remained so for 2h, before recovering to baseline; heat shock protein 27 (HSP27) was significantly decreased at hypoglycemia (p < 0.05) with subsequent recovery to baseline values
MAPKAPK5 increased at hypoglycemia (p < 0.05) and normalized thereafter (Figure 3A); DnaJ homolog subfamily B member 1 (DNAJB1) was decreased at 30-min and 1-h posthypoglycemia (p < 0.05), normalizing thereafter (Figure 3B); Stress-induced-phosphoprotein 1 (STIP1) was decreased at 30-min post-hypoglycemia (p < 0.05) and remained decreased throughout the 24-h follow up period (Figure 3C); Ubiquitin protein ligase (E3) ubiquitin-protein ligase CHIP (STUB1) was unchanged throughout the study time course (Figure 3D), as was the ubiquitin pathway protein, Ubiquitin-conjugating enzyme Ubiquitin conjugating enzyme 2 (E2) G2 (UBE2G2) (Figure 3E); the other ubiquitin pathway proteins, UBE2L3 and Ubiquitin-conjugating enzyme E2 N (UBE2N), both decreased at 30-min posthypoglycemia (p < 0.05) and remained so throughout the 24-h follow up period (Figures 3F,G)

Summary

Introduction

Climate change represents a global threat, with [1] increasing temperatures and frequent extreme weather events directly affecting humans. Climate change negatively impacts the animals and crops that are needed to sustain an increasing human population. HS has been shown to lower blood glucose levels to 2.5 mmol/l (45 mg/dl) and results in upregulation of heat shock proteins (HSPs), eliciting the heat shock response (HSR) of which HSP90, 70 and 27 have been shown to be protective. It is unclear if the HSP response is blunted by decreased glucose, thereby preventing adaptive mechanisms.

Methods

Results

Conclusion