title: Effects of genistein and estrogen on the genioglossus in rats exposed to chronic intermittent hypoxia may be HIF-1α dependent.
abstract: OBJECTIVE
  Chronic intermittent hypoxia (CIH) is a frequent feature of OSAHS. The present study was designed to evaluate the effects of genistein and estrogen on genioglossus contractile and regeneration properties in CIH rats and investigate the involvement of HIF-1α.
  
  
  METHODS
  Ovariectomized female rats were exposed to CIH for 5 weeks. Genistein and estrogen were administered by intraperitoneal injection. The genioglossus myoblasts of rat were also isolated and cultured in vitro, and the HIF-1α shRNA lentivirus was used.
  
  
  RESULTS
  Muscle fatigue resistance and myogenic regeneration were significantly decreased after CIH but were partially reversed by estrogen and genistein treatment. The effect of estrogen was more powerful than that of genistein. Compared with control group, RT-PCR and western blotting showed higher levels of HIF-1α mRNA and protein in the CIH group, but estrogen and genistein treatment reduced the levels of HIF-1α mRNA and protein in rats exposed to CIH. In genioglossus myoblasts, the expression of HIF-1α was up-regulated under hypoxia rather than normoxia and decreased over time under both hypoxia and normoxia during myogenic differentiation. HIF-1α knockdown relieved myogenesis inhibition under hypoxia.
  
  
  CONCLUSIONS
  We concluded that genistein and estrogen may inhibit the overexpression of HIF-1α induced by CIH and improve the endurance and regeneration of the genioglossus muscle.
authors.affiliation: Department of Orthodontics, Stomatology School of Tongji University, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004967:Estrogens / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D019833:Genistein / Q000008:administration & dosage / Q000494:pharmacology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D016086:Lentivirus / Q000235:genetics; D009119:Muscle Contraction / Q000187:drug effects; D024510:Muscle Development / Q000187:drug effects; D018763:Muscle Fatigue / Q000187:drug effects; D017570:MyoD Protein / Q000187:drug effects; D032448:Myoblasts, Skeletal / Q000187:drug effects; D051787:Myogenic Regulatory Factor 5 / Q000187:drug effects; D018995:Myosin Heavy Chains / Q000187:drug effects; D010052:Ovariectomy; D010609:Pharyngeal Muscles / Q000187:drug effects*; D048789:Phytoestrogens / Q000008:administration & dosage / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects; D020181:Sleep Apnea, Obstructive / Q000503:physiopathology*
chemical_list: D004967:Estrogens; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017570:MyoD Protein; D051787:Myogenic Regulatory Factor 5; D048789:Phytoestrogens; D034741:RNA, Small Interfering; D019833:Genistein; D018995:Myosin Heavy Chains
keywords: HIF-1α; chronic intermittent hypoxia; estrogen; genioglossus; genistein