【招待講演】 A single bout of heat stress increases Nrf2 and its target genes in mouse skeletal muscle

Experimental Biology 2017 (Annual Meeting of American Physiological Society)

In recent years, we have reported that heat stress induces various skeletal muscle adaptations (e.g. mitochondria, autophagy, unfolded protein response). In this study, we explored further possibilities of muscle adaptations by heat stress treatment using transcriptome approach and subsequent bioinformatics analysis. Immediately after treatment and three hours after a single bout of heat stress treatment (exposing mouse into a hot environment chamber; 40°C, 30 min), gastrocnemius muscles were collected and then examined changes in over 39,000 genes expression using Affimetrix microarray GeneChip. Consequently, we analyzed with bioinformatics algorithms TFactS and BioCarta to predict activated transcriptional factors and activated pathways, respectively. These computational analyses based on transcriptome data indicated that heat stress activates Nrf2 (Nfe2l2), a master transcriptional factor of antioxidant response, in skeletal muscle (TFactS: P<0.05; BioCarta: Fold Enrichment=7.2, P<0.05). We further confirmed by qPCR that heat stress increased Nrf2 (+39.4%, P<0.05) and its target genes such as Cat (+30.9%, P<0.05), Hmox1 (+182.6%, P<0.05), Gclc (+53.8%, P<0.05), Gclm (+32.1%, P<0.05), Gpx1 (+23.7%, P=0.07), Mt1a (+251.6%, P<0.05) and Sod1 (+27.8%, P<0.05) at 3h after treatment. Notably, there were non-detectable changes in oxidative stress marker (4HNE-conjugated protein) and gene expression of Nrf2-independently inducible antioxidant enzyme (Sod2) at both immediately post-treatment and 3h after treatment. Our observations suggest that the physiological significance of Nrf2 activation by heat stress may be other than defending oxidative stress.

Yuki Tamura, Yu Kitaoka, Koichi Nakazato, and Hideo Hatta,