S-nitrosylation of c-Jun N-terminal kinase mediates pressure overload-induced cardiac dysfunction and fibrosis

Zhou, Miao; Chen, Jiyu; Chao, Meng‐Lin; Zhang, Chao; Shi, Z.B.; Zhou, Xuechun; Xie, Liping; Sun, Shixiu; Huang, Zhengrong; Luo, Shuang; Ji, Yong

doi:10.1038/s41401-021-00674-9

Cited by 6 publications

(4 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A number of studies have shown that many fibrosis diseases are induced by high expression of JUN, 38 such as JUN related to pulmonary fibrosis and liver fibrosis 39–41 . Other reports have shown that JUN leads to myocardial fibrosis by inducing the transcription activity of AP‐1, 42 and myocardial fibrosis leads to the occurrence of AF 43 . As we know, there is no direct report on JUN and AF at present.…”

Section: Discussionmentioning

confidence: 99%

Construction of atrial fibrillation‐related circRNA/lncRNA‐miRNA‐mRNA regulatory network and analysis of potential biomarkers

Wen

Ruan

Wang

et al. 2023

Clinical Laboratory Analysis

View full text Add to dashboard Cite

Background The specific pathogenesis of atrial fibrillation (AF) remains unclear. In this study, we examined the expression of differential messenger RNAs (mRNAs), circular RNAs (circRNAs), and long‐stranded noncoding RNAs (lncRNAs) from human peripheral blood mononuclear cells to initially construct a circRNA/lncRNA‐miRNA‐mRNA ceRNA regulatory network to explore the pathogenesis of AF and to screen for potential biomarkers. Methods A total of four pairs of AF cases and healthy subjects were selected to detect differentially expressed mRNAs, circRNAs, and lncRNAs in peripheral blood mononuclear cells by microarray analysis. And 20 pairs of peripheral blood from AF patients and healthy subjects were selected for validation of mRNA, circRNA, and lncRNA by quantitative real‐time PCR (qRT‐PCR).The relevant ceRNA networks were constructed by GO and KEGG and correlation analysis. Results The results showed that compared with healthy subjects, there were 813 differentially expressed mRNAs (DEmRNAs) in peripheral blood monocytes of AF, including 445 upregulated genes and 368 downregulated genes, 120 differentially expressed circRNAs (DEcircRNAs), including 65 upregulated and 55 downregulated, 912 differentially expressed lncRNAs (DElncRNAs), including 531 upregulated and 381 downregulated lncRNAs. GO and KEGG analysis of DERNA revealed the biological processes and pathways involved in AF. Based on microarray data and predicted miRNAs, a ceRNA network containing 34 mRNAs, 212 circRNAs, 108 lncRNAs, and 38 miRNAs was constructed. Conclusion We revealed a novel ceRNA network in AF and showed that downregulated XIST, circRNA_2773, and CADM1 were negatively correlated with miR‐486‐5p expression and had a potential targeting relationship with miR‐486‐5p.

show abstract

Section: Discussionmentioning

confidence: 99%

Construction of atrial fibrillation‐related circRNA/lncRNA‐miRNA‐mRNA regulatory network and analysis of potential biomarkers

Wen

Ruan

Wang

et al. 2023

Clinical Laboratory Analysis

View full text Add to dashboard Cite

show abstract

“…NO derived from three isoforms of NOS (nNOS, iNOS and eNOS) can induce protein SNO [38], while Trx and GSNOR are the other two important enzymes known to affect the SNO of targeted proteins in a denitrosylation manner [39][40][41]. We previously reported that the aberrant SNO of different proteins during cardiac remodeling was disparate in cardiomyocytes and cardiac fibroblasts [6,42]. Interestingly, we showed here that the elevated SNO-Hsp90 levels were due to the downregulated expression of GSNOR in cardiomyocytes, while it was induced by upregulated iNOS expression in cardiac fibroblasts under pathological conditions according to our recent study [31].…”

Section: Discussionmentioning

confidence: 99%

S-nitrosylation of Hsp90 promotes cardiac hypertrophy in mice through GSK3β signaling

et al. 2021

Self Cite

View full text Add to dashboard Cite

Cardiac hypertrophy, as one of the major predisposing factors for chronic heart failure, lacks effective interventions. Exploring the pathogenesis of cardiac hypertrophy will reveal potential therapeutic targets. S-nitrosylation is a kind of posttranslational modification that occurs at active cysteines of proteins to mediate various cellular processes. We here identified heat shock protein 90 (Hsp90) as a highly S-nitrosylated target in the hearts of rodents with hypertrophy, and the role of Hsp90 in cardiac hypertrophy remains undefined. The S-nitrosylation of Hsp90 (SNO-Hsp90) levels were elevated in angiotensin II (Ang II)-or phenylephrine (PE)treated neonatal rat cardiomyocytes (NRCMs) in vitro as well as in cardiomyocytes isolated from mice subjected to transverse aortic constriction (TAC) in vivo. We demonstrated that the elevated SNO-Hsp90 levels were mediated by decreased S-nitrosoglutathione reductase (GSNOR) expression during cardiac hypertrophy, and delivery of GSNOR adeno-associated virus expression vectors (AAV9-GSNOR) decreased the SNO-Hsp90 levels to attenuate cardiac hypertrophy. Mass spectrometry analysis revealed that cysteine 589 (Cys589) might be the S-nitrosylation site of Hsp90. Delivery of the mutated AAV9-Hsp90-C589A inhibited SNO-Hsp90 levels and attenuated cardiac hypertrophy. We further revealed that SNO-Hsp90 led to increased interaction of glycogen synthase kinase 3β (GSK3β) and Hsp90, leading to elevated GSK3β phosphorylation and decreased eIF2Bε phosphorylation, thereby aggravating cardiac hypertrophy. Application of GSK3β inhibitor TWS119 abolished the protective effect of Hsp90-C589A mutation in Ang II-treated NRCMs. In conclusion, this study demonstrates a critical role of SNO-Hsp90 in cardiac hypertrophy, which may be of a therapeutic target for cardiac hypertrophy treatment.

show abstract

“… 1404 SNO at C116/C163 of JNK accelerates cardiac fibrosis. 1405 SNO of Hsp90 affects cardiac hypertrophy and myocardial fibrosis. A recent study found that SNO of C521 of Hsp90 can inhibit the interaction between Hsp90 and AHA1, promote the recruitment of CDC37, and aggravate atherosclerosis.…”

Section: Redox Modificationsmentioning

confidence: 99%

“…Cardiac fibrosis is an irreversible pathological process, and inhibition of SNO of Hsp90 can alleviate myocardial fibrosis through the TGFβ/SMAD3 signaling pathway (Figure 24). 1404 SNO at C116/C163 of JNK accelerates cardiac fibrosis 1405 . SNO of Hsp90 affects cardiac hypertrophy and myocardial fibrosis.…”

Section: Redox Modificationsmentioning

confidence: 99%

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Zhong

Xiao

Xie

et al. 2023

MedComm

View full text Add to dashboard Cite

Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on the backbones or amino acid side chains of proteins and expand the diversity of proteins, which provides the basis for the emergence of organismal complexity. To date, more than 650 types of protein modifications, such as the most well‐known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short‐chain and long‐chain acylation modifications, redox modifications, and irreversible modifications, have been described, and the inventory is still increasing. By changing the protein conformation, localization, activity, stability, charges, and interactions with other biomolecules, PTMs ultimately alter the phenotypes and biological processes of cells. The homeostasis of protein modifications is important to human health. Abnormal PTMs may cause changes in protein properties and loss of protein functions, which are closely related to the occurrence and development of various diseases. In this review, we systematically introduce the characteristics, regulatory mechanisms, and functions of various PTMs in health and diseases. In addition, the therapeutic prospects in various diseases by targeting PTMs and associated regulatory enzymes are also summarized. This work will deepen the understanding of protein modifications in health and diseases and promote the discovery of diagnostic and prognostic markers and drug targets for diseases.

show abstract

S-nitrosylation of c-Jun N-terminal kinase mediates pressure overload-induced cardiac dysfunction and fibrosis

Cited by 6 publications

References 46 publications

Construction of atrial fibrillation‐related circRNA/lncRNA‐miRNA‐mRNA regulatory network and analysis of potential biomarkers

Construction of atrial fibrillation‐related circRNA/lncRNA‐miRNA‐mRNA regulatory network and analysis of potential biomarkers

S-nitrosylation of Hsp90 promotes cardiac hypertrophy in mice through GSK3β signaling

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Contact Info

Product

Resources

About