Contribution of IL-10 to the endoplasmic reticulum stress response in the skeletal muscle of trained mice.

• Grant number: 24/06145-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2024
• End date: December 31, 2025
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Adelino Sanchez Ramos da Silva
• Grantee: Júlia Teixeira Marinho
• Host Institution: Escola de Educação Física e Esporte de Ribeirão Preto (EEFERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 19/11820-5 - Nr1d1 function on the aging-associated Sarcopenia, AP.TEM

Abstract

Skeletal muscle is the most comprehensive tissue in the human body, comprising about 40% of total body weight and 50-75% of all proteins in the body. The series position of its sarcomeres results in muscle contraction, which involves a series of chemical processes that require an optimal concentration of calcium (Ca²z) in the lumen of the endoplasmic reticulum (ER). The ER is an intracellular organelle responsible for handling Ca²z, lipid synthesis, folding and translation of proteins properly. However, when there is an imbalance in homeostasis and, consequently, a failure of the actions mentioned above, endoplasmic reticulum (ER) stress occurs, which can lead to cell apoptosis. To reverse this process, cells activate the unfolded protein response (UPR), helping to restore proper ER function. A non-pharmacological tool that can mediate responses linked to UPR is chronic physical exercise, acting as a protective mechanism against current and future stress. Furthermore, an anti-inflammatory cytokine that has gained notoriety for its ER stress inhibitory role is interleukin-10 (IL-10), playing a central role in the control of immune and adaptive responses. Therefore, the objective of the present project is to verify the role of IL-10 in ER stress in skeletal muscle and the effect of the resistance exercise protocol on the UPR pathway in wild-type (WT) and IL-1 knockout (KO) animals. 10. Six-week-old C57BL/6 mice and IL10-/- mice will be used, which will be obtained from the Jackson Laboratory, bred and used as the IL-10 KO group. The WT and KO mice will be distributed into two subgroups for each phenotype (n=5/group): Control (CT; sedentary) and Exercise (EX; submitted to the resistance exercise protocol). After determining 1RM in the ladder climbing exercise, the animals will perform a resistance protocol. This training will be carried out three times a week, over 8 weeks. ER inflammation and stress will be quantified using the RT-qPCR technique.