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The role of aldehyde dehydrogenase 2 and reactive aldehydes on the anabolic responses, satellite cell activation and recovery from muscle damage in response to strength training: a study with ALDH2 gene mutation carriers

Grant number: 22/05145-6
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): August 01, 2023
Effective date (End): July 31, 2026
Field of knowledge:Health Sciences - Physical Education
Principal Investigator:Fabiana Braga Benatti
Grantee:Wagner Ribeiro Pereira
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):23/16360-8 - Impact of the ACTN3 and ALDH2 gene polymorphisms on skeletal muscle phenotypes in response to exercise and anabolic steroid use, BE.EP.DD

Abstract

Aldehyde dehydrogenase 2 (ALDH2) is an important enzyme involved in reactive aldehydes detoxification processes. About 40% of Asian population carry a mutation in the ALDH2 gene, which can reduce ALDH2 enzyme activity, thereby affecting reactive aldehydes detoxification. Recent evidence indicate that aldehydes from lipid peroxidation can impair satellite cell activation, which are myogenic stem cell present in skeletal muscle and are involved in tissue repair from muscle damage. Recent studies have also suggested that histidine-containing dipeptides, such as carnosine, can scavenge reactive aldehydes via carnosine-aldehyde adduct formation. The aim of this study is to evaluate whether individuals with ALDH2 gene mutation have impaired anabolic and damage-repairing responses to strength exercise. Forty Asian descent men will participate in this study. They will be separated in two groups according to their ALDH2 genotype: those with reduced ALDH2 enzyme activity (heterozygous - ALDH2*1/*2; homozygous - ALDH2*2/*2; n=20) and those with normal ALDH2 enzyme activity (homozygous - ALDH2*1/*1; n=20). The participants will be evaluated for lower limb maximal dynamic strength (1RM test for leg-press), maximum voluntary isometric contraction, body composition and food intake. Venous blood samples will be collected for genomic DNA isolation and genotyping, for the determination of the muscle enzymes creatine kinase (CK) and lactate dehydrogenase (LDL), and also to measure acetaldehyde levels after an ingestion of alcoholic beverage. Carnosine-aldehydes adducts will be quantified in urine samples. Muscle samples will be taken vastus lateralis using biopsy procedures to analyze the following parameters: satellite cell activation, molecular pathways of protein synthesis activation, sarcomere integrity, ALDH2 enzyme activity, mitochondrial function, intramuscular carnosine content, carnosine-aldehydes adducts levels in skeletal muscle. Participants will undertake one strength exercise session of the lower limbs to induce muscle damage, after which these same parameters will be evaluated again following the session. Data will be analyzed using mixed models. Statistical significance adopted will be p <0.05. (AU)

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