Estrogen protects against acidosis-mediated articular chondrocyte injury by promoting ASIC1a protein degradation

Su, Jingwen; Li, Shufang; Tao, Jingjing; Xu, Yayun; Wang, Ke; Qian, Xuewen; Deng, Guangcun; Peng, Xiaoqing; Chen, Feihu

doi:10.1016/j.ejphar.2021.174381

Cited by 9 publications

(11 citation statements)

References 38 publications

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“…The two female patients in our study displayed atrial arrhythmias at the beginning, which exacerbated the heart failure significantly. The gender-associated difference in clinical manifestations may be due to estrogen, which promotes autophagy and a lysosome pathway in multiple cells ( 24 ).…”

Section: Discussionmentioning

confidence: 99%

Case Report: Danon Disease: Six Family Members and Literature Review

Wang

Jia

Guo

et al. 2022

Front. Cardiovasc. Med.

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Danon disease is a rare X-linked dominant genetic disorder that manifests with a clinical triad of cardiomyopathy, skeletal myopathy, and intellectual disability. It is caused by mutations in the lysosome-associated membrane 2 (LAMP2) gene. We report one case of Danon disease and his family members, characterized by ventricular pre-excitation, ventricular hypertrophy, abnormal muscle enzymes, and aberrant liver function. All the patients were confirmed to have Danon disease through genetic screening. Relevant literature was reviewed as a reference for the diagnosis and treatment of the disease.

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Section: Discussionmentioning

confidence: 99%

Case Report: Danon Disease: Six Family Members and Literature Review

Wang

Jia

Guo

et al. 2022

Front. Cardiovasc. Med.

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“…Owing to the vital physiological roles of mitochondria, which are essential for apoptosis, strategies capable of inhibiting mitochondrial damage pathways in a drug-controllable manner are particularly promising for RA treatment. Previous studies have demonstrated that estradiol induced ASIC1a protein degradation through the estrogenrelated receptor-alpha (Esrra) and G-protein coupled estradiol receptor 1 (GPER1) receptors, the mechanisms of which might be related to the Esrra-AMPK-ULK1 and PI3K-GPER1-AKT-mTOR signaling pathways (Figure 6), to protect chondrocytes and rats with AA from acid-induced apoptosis, damage, and autophagy [16,17]. Estradiol treatment led to the downregulation of ASIC1a proteins in a time-and dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

“…In vivo, the ASIC1a-specific inhibitor PcTx-1 had a significant protective effect on rat articular cartilage [14,15]. Our previous research found that estrogen promotes the degradation of the ASIC1a protein via the autophagy-lysosomal pathway and further prevents acidosis-induced chondrocyte death [16,17]. However, the mechanism by which ASIC1a-induced Ca 2+ influx leads to chondrocyte death remains to be explored.…”

Section: Introductionmentioning

confidence: 99%

Estrogen antagonizes ASIC1a-induced chondrocyte Mitochondrial stress in Rheumatoid Arthritis

Zai

Qian

et al. 2022

Preprint

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Destruction of articular cartilage and bone is the main cause of joint dysfunction in rheumatoid arthritis. Estrogen has been proven to have a protective effect against articular cartilage damage, however, the underlying mechanisms remain unclear. Here, we found that acid-sensing ion channel 1a (ASIC1a) mediates intracellular Ca2+ overload in response to extracellular acidification, which leads to mitochondrial stress in rat chondrocytes. Estrogen antagonizes Ca2+ overload-induced mitochondrial stress by inhibiting the activity of ASIC1a, thereby protecting articular chondrocytes in vivo and in vitro . These findings suggest that extracellular acidification induces mitochondrial stress by activating ASIC1a, leading to the death of rat articular chondrocytes. Estrogen is a beneficial factor that antagonizes acidosis-induced joint damage by inhibiting ASIC1a activity. In summary, our study provides new insights into the protective effect and mechanism of action of estrogen in rheumatoid arthritis.

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“…The increased incidence of RA in postmenopausal women may be related to the lack of estrogen. Studies have found that estrogen can promote the degradation of acid-sensitive ion channel 1a protein and inhibit the cytotoxicity of acidosis through autophagy-lysosome-dependent pathways, thereby protecting chondrocytes ( 62 , 63 ).…”

Section: The Potential Connection Between Dna Methylation Of Cd4+ T C...mentioning

confidence: 99%

DNA Methylation of T Lymphocytes as a Therapeutic Target: Implications for Rheumatoid Arthritis Etiology

et al. 2022

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Rheumatoid arthritis (RA) is an autoimmune disease that can cause joint damage and disability. Epigenetic variation, especially DNA methylation, has been shown to be involved in almost all the stages of the pathology of RA, from autoantibody production to various self-effector T cells and the defects of protective T cells that can lead to chronic inflammation and erosion of bones and joints. Given the critical role of T cells in the pathology of RA, the regulatory functions of DNA methylation in T cell biology remain unclear. In this review, we elaborate on the relationship between RA pathogenesis and DNA methylation in the context of different T cell populations. We summarize the relevant methylation events in T cell development, differentiation, and T cell-related genes in disease prediction and drug efficacy. Understanding the epigenetic regulation of T cells has the potential to profoundly translate preclinical results into clinical practice and provide a framework for the development of novel, individualized RA therapeutics.

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Estrogen protects against acidosis-mediated articular chondrocyte injury by promoting ASIC1a protein degradation

Cited by 9 publications

References 38 publications

Case Report: Danon Disease: Six Family Members and Literature Review

Case Report: Danon Disease: Six Family Members and Literature Review

Estrogen antagonizes ASIC1a-induced chondrocyte Mitochondrial stress in Rheumatoid Arthritis

DNA Methylation of T Lymphocytes as a Therapeutic Target: Implications for Rheumatoid Arthritis Etiology

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