Aldehyde dehydrogenase 2 alleviates monosodium iodoacetate-induced oxidative stress, inflammation and apoptosis in chondrocytes via inhibiting aquaporin 4 expression

Abstract

Background Knee osteoarthritis (KOA) is a common cause of disability among the elderly. We aimed to explore the effects of aldehyde dehydrogenase (ALDH) 2 on the progression of KOA and identifying the potential mechanisms. Methods First, ALDH2 expression in knee joint effusion of patients with KOA and the levels of oxidative stress-related markers were determined. After ALDH2 overexpression in monosodium iodoacetate (MIA)-treated SW1353 cells, cell viability was tested with CCK-8 assay. Subsequently, oxidative stress and inflammation-associated factors were measured. Meanwhile, cell apoptosis was assessed with TUNEL staining and expression of apoptosis-related proteins was detected by western blotting. To analyze the mechanism of ALDH2 in KOA, aquaporin 4 (AQP4) expression was determined using western blotting following ALDH2-upregulation. Subsequently, AQP4 was overexpressed to evaluate the changing of oxidative stress, inflammation and apoptosis in SW1353 cells exposed to MIA with ALDH2 overexpression. Results Results indicated that knee joint effusion with higher ALDH2 expression displayed lower oxidative stress. In addition, significantly upregulated ALDH2 expression was observed in MIA-treated SW1353 cells. ALDH2 overexpression oxidative stress, inflammation and apoptosis in SW1353 cells exposed to MIA. Moreover, MIA-triggered elevated expression of AQP4, which was reduced by ALDH2 overexpression. By contrast, AQP4-upregulation abrogated the inhibitory effects of ALDH2 on oxidative stress, inflammation and apoptosis in MIA-induced SW1353 cells. Conclusions ALDH2 inactivates the expression of AQP4, by which mechanism the MIA-induced oxidative stress, inflammation and apoptosis injuries were alleviated, which provides a novel insight for understanding the mechanism of KOA and a promising target for the treatment of this disease.

Calycosin protects against oxidative stress‐induced cardiomyocyte apoptosis by activating aldehyde dehydrogenase 2

“…In vivo, our study established that Calycosin has anti-apoptotic effects in an MI animal model. These findings corroborated recent findings that reported that Calycosin reduced myocardial apoptosis in a model of cardiac damage induced by doxorubicin (Lu, Lu, Gao, Wang, & Wang, 2021;Zhai et al, 2020) or isoproterenol (Cheng, Zhao, Tse, Le, & Rong, 2015; Huang Khan et al, 2022;Pan et al, 2021), including MI. ALDH2 activation has been shown to enhance anti-oxidative capacity of cells, which is involved in scavenging harmful aldehydes such as MDA and 4-HNE, resulting in a decrease in cellular ROS generation (Islam et al, 2021;Zhang et al, 2018).…”

“…ALDH2, a mitochondrial protein enzyme that is highly expressed in the heart, is the key enzyme responsible for the detoxification of toxic aldehydes in the heart. Numerous studies have established that ALDH2 deficiency or dysregulation is frequently associated with a variety of oxidative stress‐induced diseases (He et al, 2021; Ji et al, 2021; Khan et al, 2022; Pan et al, 2021), including MI. ALDH2 activation has been shown to enhance anti‐oxidative capacity of cells, which is involved in scavenging harmful aldehydes such as MDA and 4‐HNE, resulting in a decrease in cellular ROS generation (Islam et al, 2021; Zhang et al, 2018).…”

Dissecting Regulators of Aging and Age-Related Macular Degeneration in the Retinal Pigment Epithelium

“…Mitochondrial ALDH2 ( Figure 3(c) , spot #D20) is essential for the removal of toxic aldehydes that are by-products of lipid peroxidation in the RPE [ 52 ]. In a recent study, overexpression of ALDH2 restored retinal function by reducing apoptosis and enhancing chaperone activity in mice [ 53 ]. Glutamine synthetase is an enzyme that generates glutamine via the condensation of glutamate and ammonia.…”

Lipid peroxidation in osteoarthritis: focusing on 4-hydroxynonenal, malondialdehyde, and ferroptosis

“…Ausra et al [ 87 ] showed that ALDH2 may play a protective role in human OA chondrocytes. Moreover, a recent study demonstrated that ALDH2 could alleviate MIA‑induced oxidative stress, inflammation and apoptosis in chondrocytes via inhibiting aquaporin 4 expression [ 88 ].…”