title: A FoxO1-dependent, but NRF2-independent induction of heme oxygenase-1 during muscle atrophy.
abstract: Skeletal muscle plays key roles in metabolic homeostasis. Loss of muscle mass, called muscle atrophy exacerbates disease-associated metabolic perturbations. In this study, we characterized the molecular functions and mechanisms underlying regulation of skeletal muscle atrophy induced by denervation. Denervation significantly increased the expression of heme oxygenase-1 (HO-1) and atrogenes in skeletal muscle. Forkhead box protein O1 (FoxO1) drastically increased in atrophied muscle and selectively stimulated HO-1 gene transcription through direct DNA binding. Lack of HO-1 substantially attenuated muscle atrophy, whereas HO-1 overexpression caused muscle damage in vitro and in vivo. Collectively, HO-1 induced by FoxO1 may cause skeletal muscle atrophy.
authors.affiliation: College of Pharmacy and Global Top5 Research Program, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Jione
authors.initials: J
authors.lastname: Kang
authors.affiliation: College of Pharmacy and Global Top5 Research Program, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Mi Gyeong
authors.initials: MG
authors.lastname: Jeong
authors.affiliation: College of Pharmacy and Global Top5 Research Program, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Sera
authors.initials: S
authors.lastname: Oh
authors.affiliation: College of Pharmacy and Global Top5 Research Program, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Jang
authors.affiliation: College of Pharmacy and Global Top5 Research Program, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Hyo Kyeong
authors.initials: HK
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Global Top5 Research Program, Ewha Womans University, Seoul 120-750, Republic of Korea. Electronic address: eshwang@ewha.ac.kr.
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Hwang
mesh_terms: D000818:Animals; D002460:Cell Line; D003714:Denervation; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008957:Models, Genetic; D018482:Muscle, Skeletal / Q000294:innervation / Q000378:metabolism; D009133:Muscular Atrophy / Q000235:genetics / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000293:injuries / Q000503:physiopathology
chemical_list: D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D051547:Heme Oxygenase-1
keywords: FoxO1; MAFbx; MuRF1; NRF2; Nerve injury