Open Access

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
  • View Affiliations

  • 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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June-2020
Volume 45 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Zhang XH, Wu JX, Sha JZ, Yang B, Sun JR and Bao ED: Heat shock protein 90 relieves heat stress damage of myocardial cells by regulating Akt and PKM2 signaling in vivo. Int J Mol Med 45: 1888-1908, 2020.
APA
Zhang, X., Wu, J., Sha, J., Yang, B., Sun, J., & Bao, E. (2020). Heat shock protein 90 relieves heat stress damage of myocardial cells by regulating Akt and PKM2 signaling in vivo. International Journal of Molecular Medicine, 45, 1888-1908. https://doi.org/10.3892/ijmm.2020.4560
MLA
Zhang, X., Wu, J., Sha, J., Yang, B., Sun, J., Bao, E."Heat shock protein 90 relieves heat stress damage of myocardial cells by regulating Akt and PKM2 signaling in vivo". International Journal of Molecular Medicine 45.6 (2020): 1888-1908.
Chicago
Zhang, X., Wu, J., Sha, J., Yang, B., Sun, J., Bao, E."Heat shock protein 90 relieves heat stress damage of myocardial cells by regulating Akt and PKM2 signaling in vivo". International Journal of Molecular Medicine 45, no. 6 (2020): 1888-1908. https://doi.org/10.3892/ijmm.2020.4560