Abstract
Although chronic intermittent hypoxia- (IH-) induced myocardial apoptosis is an established pathophysiological process resulting in a poor prognosis for patients with obstructive sleep apnea syndrome, its underlying mechanism remains unclear. This study is aimed at exploring the role of makorin ring finger protein 1 (MKRN1) in IH-induced myocardial apoptosis and elucidating its molecular activity. First, the GSE2271 dataset was downloaded from the Gene Expression Omnibus database to identify the differentially expressed genes. Then, an SD rat model of IH, together with rat cardiomyocyte H9C2 and human cardiomyocyte AC16 IH models, was constructed. TUNEL, Western blot, and immunohistochemistry assays were used to detect cell apoptosis. Dihydroethidium staining was conducted to analyze the concentration of reactive oxygen species. In addition, RT-qPCR, Western blot, and immunohistochemistry were performed to measure the expression levels of MKRN1 and p21. The direct interaction between MKRN1 and p21 was determined using coimmunoprecipitation and ubiquitination analysis. MKRN1 expression was found to be downregulated in IH rat myocardial tissues as well as in H9C2 and AC16 cells. Upregulated expression of MKRN1 in H9C2 and AC16 cells alleviated the IH-induced reactive oxygen species production and cell apoptosis. Mechanistically, MKRN1 promoted p21 protein ubiquitination and the proteasome pathway degradation to negatively regulate p21 expression. Thus, MKRN1 regulates p21 ubiquitination to prevent IH-induced myocardial apoptosis.
Highlights
Obstructive sleep apnea (OSA) syndrome is a disorder mainly characterized by chronic intermittent hypoxia (IH) induced by repeated pharyngeal collapse during sleep
Myocardial apoptosis is the early manifestation of intermittent hypoxia- (IH-)induced myocardial injury [2], reactive oxygen species (ROS) plays an important role in cardiovascular injury, and inhibition of ROS can effectively alleviate cardiovascular injury
Coculture of selenoprotein silencing arterial endothelial cells and neutrophils increased neutrophil extracellular trap formation, while acetylcysteine reversed the increase of neutrophil extracellular trap formation induced by selenoprotein silencing by inhibiting ROS burst [15]
Summary
Obstructive sleep apnea (OSA) syndrome is a disorder mainly characterized by chronic intermittent hypoxia (IH) induced by repeated pharyngeal collapse during sleep. It has been shown that increases in IH severity and duration can lead to myocardial apoptosis injury [3], which contributes to CVD complications in OSA patients. OSA-related excessive reactive oxygen species (ROS) production, chronic inflammation, endoplasmic reticulum stress, activation of hypoxiainducible factor 1 (HIF-1) expression, and mitochondrial dysfunction can result in myocardial apoptosis [4]. Among these factors, excessive ROS production induced by a repeated hypoxia-reoxygenation cycle is considered the predominant cause of IH-induced myocardial apoptosis. Suppressing excess ROS production to reduce IH-induced myocardial apoptosis is considered a promising treatment direction
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
