Genetic ablation of Toll-like Receptor 4 seems to activate the apoptosis pathway in the skeletal muscle of mice after acute physical exercise

Author(s)

Marafon, Bruno B. ; Pinto, Ana P. ; de Vicente, Larissa G. ; da Rocha, Alisson L. ; Simabuco, Fernando M. ; Ropelle, Eduardo R. ; de Moura, Leandro P. ; Cintra, Dennys E. ; Pauli, Jose R. ; da Silva, Adelino S. R.

• Document type: Journal article
• Source: Cell Biochemistry and Function; v. N/A, p. 12-pg., 2022-11-22.

Abstract

Many conditions, such as inflammation and physical exercise, can induce endoplasmic reticulum (ER) stress. Toll-like Receptor 4 (TLR4) can trigger inflammation and ER stress events. However, there are still no data in the literature regarding the role of TLR4 in ER stress during exercise in skeletal muscle. Therefore, the current investigation aimed to verify the responses of ER stress markers in wild-type (WT) and Tlr4 global knockout (KO) mice after acute and chronic physical exercise protocols. Eight-week-old male WT and KO mice were submitted to acute (moderate or high intensity) and chronic (4-week protocol) treadmill exercises. Under basal conditions, KO mice showed lower performance in the rotarod test. Acute high-intensity exercise increased eIF2 alpha protein in the WT group. After the acute high-intensity exercise, there was an increase in Casp3 and Ddit3 mRNA for the KO mice. Acute moderate exercise increased the cleaved Caspase-3/Caspase-3 in the KO group. In response to chronic exercise, the KO group showed no improvement in any performance evaluation. The 4-week chronic protocol did not generate changes in ATF6, CHOP, p-IRE1 alpha, p-eIF2 alpha/eIF2 alpha, and cleaved Caspase-3/Caspase-3 ratio but reduced BiP protein compared with the KO-Sedentary group. These results demonstrate the global deletion of Tlr4 seems to have the same effects on UPR markers of WT animals after acute and chronic exercise protocols but decreased performance. The cleaved Caspase-3/Caspase-3 ratio may be activated by another pathway other than ER stress in Tlr4 KO animals. (AU)

• FAPESP's process: 20/13443-1 - Implications of aerobic exercise on the Notch 1 signaling pathway and regulation of lipogenesis and gluconeogenesis in the liver
• Grantee: José Rodrigo Pauli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/04269-8 - Role of TLR4 in endoplasmic reticulum stress induced by physical exercise in skeletal muscle
• Grantee: Bruno Brieda Marafon
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 19/11820-5 - Nr1d1 function on the aging-associated Sarcopenia
• Grantee: Adelino Sanchez Ramos da Silva
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 21/06291-3 - Multi-user Equipament approved in grant 2019/11820-5: ChemiDoc Imaging System and accessories
• Grantee: Adelino Sanchez Ramos da Silva
• Support Opportunities: Multi-user Equipment Program