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Lactate accumulation induced genioglossus myoblast injury under hypoxia

Zhang, M.

2023-11-05 cancer biology
10.1101/2023.11.03.565480 bioRxiv
Show abstract

Obstructive sleep apnea (OSA) is an increasingly common disorder of repeated upper airway collapse during sleep, leading to chronic intermittent hypoxia and metabolic alteration such as lactate accumulation. Genioglossus (GG), the largest upper airway dilator, is of great significance in maintaining the patency of the upper airway collapse. However, the lactate mechanism in OSA/CIH models is incomplete understood. Here, extracellular and intracellular contents of lactate were detected, and found hypoxia induced lactate accumulation in GG myoblasts. The we treat GG with lactate, and found lactate inhibited myoblasts proliferation and myotubes formation under hypoxia. When the lactate efflux was blocked by monocarboxylic acid transporter 1 (MCT1, a lactate transport) inhibitor AZD3965 (AZD), the expression levels of myogenic markers MyoD, Myogenin and MyHC were reduced. In summary, lactate efflux obstruction and lactate accumulation induced GG myoblast injury under hypoxia. These findings provide a theoretical basis for regulation lactate metabolism to alleviate muscle fatigue in the treatment of OSA.

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