Heat shock protein 90 relieves heat stress damage of myocardial cells by regulating Akt and PKM2 signaling in vivo

Zhang,Xiao‑Hui; Wu,Jia‑Xin; Sha,Jun‑Zhou; Yang,Bo; Sun,Jia‑Rui; Bao,En‑Dong

doi:10.3892/ijmm.2020.4560

Heat shock protein 90 relieves heat stress damage of myocardial cells by regulating Akt and PKM2 signaling in vivo

Authors:
- Xiao‑Hui Zhang
- Jia‑Xin Wu
- Jun‑Zhou Sha
- Bo Yang
- Jia‑Rui Sun
- En‑Dong Bao
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Affiliations: Department of Basic Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu 210095, P.R. China
Published online on: March 31, 2020 https://doi.org/10.3892/ijmm.2020.4560
Pages: 1888-1908
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Heat shock protein 90 (Hsp90) is associated with resisting heat‑stress injury to the heart, particularly in myocardial mitochondria. However, the mechanism underlying this effect remains unclear. The present study was based on the high expression of Hsp90 during heat stress (HS) and involved inducing higher expression of Hsp90 using aspirin in mouse hearts. Higher Hsp90 levels inhibited HS‑induced myocardial damage and apoptosis, and mitochondrial dysfunction, by stimulating Akt (protein kinase B) activation and PKM2 (pyruvate kinase M2) signaling, and subsequently increasing mitochondrial Bcl‑2 (B‑cell lymphoma 2) levels and its phosphorylation. Functional inhibition of Hsp90 using geldanamycin verified that reducing the association of Hsp90 with Akt and PKM2 caused the functional decline of phosphorylated (p)‑Akt and PKM2 that initiate Bcl‑2 to move into mitochondria, where it is phosphorylated. Protection by Hsp90 was weakened by blocking Akt activation using Triciribine, which could not be recovered by normal initiation of the PKM2 pathway. Furthermore, increased Hsp70 levels induced by Akt activation in myocardial cells may flow into the blood to resist heat stress. The results provided in vivo mechanistic evidence that in myocardial cells, Hsp90 resists heat stress via separate activation of the Akt‑Bcl‑2 and PKM2‑Bcl‑2 signaling pathways, which contribute toward preserving cardiac function and mitochondrial homeostasis.

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