Abstract
Obstructive sleep apnea and hypopnea syndrome (OSAHS) is a clinical syndrome characterized by recurrent episodes of obstruction of the upper airway during sleep that leads to a hypoxic condition. Genioglossus, an important pharyngeal muscle, plays an important role in maintaining an open upper airway for effective breathing. Our previous study found that genistein (a kind of phytoestrogen) protects genioglossus muscle from hypoxia-induced oxidative injury. However, the underlying mechanism is still unknown. In the present study, we examined the effects of hypoxia on genioglossus myoblast proliferation, viability and apoptosis, and the protective effect of genistein and its relationship with the PI3K/Akt and ERK MAPK pathways. Cell viability and Bcl-2 were reduced under hypoxic condition, while ROS generation, caspase-3, MDA, and DNA damage were increased following a hypoxia exposure. However, the effects of hypoxia were partially reversed by genistein in an Akt- and ERK- (but not estrogen receptor) dependent manner. In conclusion, genistein protects genioglossus myoblasts against hypoxia-induced oxidative injury and apoptosis independent of estrogen receptor. The PI3K-Akt and ERK1/2 MAPK signaling pathways are involved in the antioxidant and anti-apoptosis effect of genistein on genioglossus myoblasts.
Highlights
Genistein, a soy isoflavone, is a plant-derived polyphenolic non-steroidal compound with estrogen-like biological activity without side effect for long-term use[16, 17]
Oxidative stress and genioglossus myoblast injury can be induced by Hypoxia
The levels of H2O2 was measured using dichlorofluorescein diacetate (DCF-DA) to determine whether hypoxia stimulates the generation of ROS in genioglossus myoblast
Summary
A soy isoflavone, is a plant-derived polyphenolic non-steroidal compound with estrogen-like biological activity without side effect for long-term use[16, 17]. We previously found that genistein attenuates genioglossus muscle fatigue in vivo[4, 12]. The detailed molecular mechanisms that underlie the effects of genistein on genioglossus remain to be elucidated. The PI3K/Akt and MAPK pathways regulate a variety of cellular activities including proliferation, differentiation, survival, oxidative stress, and death[18,19,20]. Genistein has been found to exert its protective effects in relation to the PI3K/Akt and MAPK pathways[21,22,23,24]. Apoptosis, and to identify the muscle protective effect of genistein and its underlying relationship with the PI3K/ Akt and MAPK pathways
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