RGS7 balances acetylation/de-acetylation of p65 to control chemotherapy-dependent cardiac inflammation

Basak, Madhuri; Das, Kiran; Mahata, Tarun; Kumar, Dinesh; Nagar, Nupur; Poluri, Krishna Mohan; Kumar, Pranesh; Das, Priyadip; Stewart, Adele; Maity, Biswanath

doi:10.1007/s00018-023-04895-5

Cited by 3 publications

(2 citation statements)

References 87 publications

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“…Nucleolin phosphorylation at T76 and T84 is required for its ability to protect against apoptosis and regulate miRNA-21 in myocytes [ 20 ], and RGS6 also modulates Nucleolin phosphorylation levels, though this may just be a secondary consequence of changes in the total pool of Nucleolin. One intriguing possibility is that, like R7 family member RGS7, which bidirectionally controls acetylation of p65 [ 57 ], RGS6/Tip60 might direct Nucleolin acetylation [ 58 ], which has been shown to influence proteasomal Nucleolin degradation [ 59 ]. We should also note that Nucleolin knockdown alone was sufficient to trigger RGS6 up-regulation indicating that Nucleolin and RGS6 directly antagonize the activity of the other.…”

Section: Discussionmentioning

confidence: 99%

RGS6 drives cardiomyocyte death following nucleolar stress by suppressing Nucleolin/miRNA-21

Sengar,

Kumar,

Rai

et al. 2024

J Transl Med

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Background Prior evidence demonstrated that Regulator of G protein Signaling 6 (RGS6) translocates to the nucleolus in response to cytotoxic stress though the functional significance of this phenomenon remains unknown. Methods Utilizing in vivo gene manipulations in mice, primary murine cardiac cells, human cell lines and human patient samples we dissect the participation of a RGS6-nucleolin complex in chemotherapy-dependent cardiotoxicity. Results Here we demonstrate that RGS6 binds to a key nucleolar protein, Nucleolin, and controls its expression and activity in cardiomyocytes. In the human myocyte AC-16 cell line, induced pluripotent stem cell derived cardiomyocytes, primary murine cardiomyocytes, and the intact murine myocardium tuning RGS6 levels via overexpression or knockdown resulted in diametrically opposed impacts on Nucleolin mRNA, protein, and phosphorylation.RGS6 depletion provided marked protection against nucleolar stress-mediated cell death in vitro, and, conversely, RGS6 overexpression suppressed ribosomal RNA production, a key output of the nucleolus, and triggered death of myocytes. Importantly, overexpression of either Nucleolin or Nucleolin effector miRNA-21 counteracted the pro-apoptotic effects of RGS6. In both human and murine heart tissue, exposure to the genotoxic stressor doxorubicin was associated with an increase in the ratio of RGS6/Nucleolin. Preventing RGS6 induction via introduction of RGS6-directed shRNA via intracardiac injection proved cardioprotective in mice and was accompanied by restored Nucleolin/miRNA-21 expression, decreased nucleolar stress, and decreased expression of pro-apoptotic, hypertrophy, and oxidative stress markers in heart. Conclusion Together, these data implicate RGS6 as a driver of nucleolar stress-dependent cell death in cardiomyocytes via its ability to modulate Nucleolin. This work represents the first demonstration of a functional role for an RGS protein in the nucleolus and identifies the RGS6/Nucleolin interaction as a possible new therapeutic target in the prevention of cardiotoxicity.

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Section: Discussionmentioning

confidence: 99%

RGS6 drives cardiomyocyte death following nucleolar stress by suppressing Nucleolin/miRNA-21

Sengar,

Kumar,

Rai

et al. 2024

J Transl Med

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“…TIP60, a member of the MYST family, remains unexplored in the context of renal fibrosis. Nevertheless, a substantial body of research underscores the pivotal role of TIP60 in diverse biological processes such as metabolism, aging, inflammation, and autophagy [ 96 , 97 , 98 , 99 ]. Studies have shown that the knockdown of TIP60 promotes ECM remodeling and attenuates cardiac fibrosis [ 96 ].…”

Section: Hats In Kidney Fibrosismentioning

confidence: 99%

Role of Histone Modifications in Kidney Fibrosis

Pan,

Yuan,

Xia

et al. 2024

Medicina

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Chronic kidney disease (CKD) is characterized by persistent kidney dysfunction, ultimately resulting in end-stage renal disease (ESRD). Renal fibrosis is a crucial pathological feature of CKD and ESRD. However, there is no effective treatment for this condition. Despite the complex molecular mechanisms involved in renal fibrosis, increasing evidence highlights the crucial role of histone modification in its regulation. The reversibility of histone modifications offers promising avenues for therapeutic strategies to block or reverse renal fibrosis. Therefore, a comprehensive understanding of the regulatory implications of histone modifications in fibrosis may provide novel insights into more effective and safer therapeutic approaches. This review highlights the regulatory mechanisms and recent advances in histone modifications in renal fibrosis, particularly histone methylation and histone acetylation. The aim is to explore the potential of histone modifications as targets for treating renal fibrosis.

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Screening and identification of key biomarkers associated with endometriosis using bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2024

Preprint

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Endometriosis is a common cause of endometrial-type mucosa outside the uterine cavity with symptoms such as painful periods, chronic pelvic pain, pain with intercourse and infertility. However, the early diagnosis of endometriosis is still restricted. The purpose of this investigation is to identify and validate the key biomarkers of endometriosis. Next generation sequencing (NGS) dataset GSE243039 was obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) between endometriosis and normal control samples were identified. After screening of DEGs, gene ontology (GO) and REACTOME pathway enrichment analyses were performed. Furthermore, a protein-protein interaction (PPI) network was constructed and modules were analysed using the Human Integrated Protein-Protein Interaction rEference (HIPIE) database and Cytoscape software, and hub genes were identified. Subsequantely, a network between miRNAs and hub genes, and network between TFss and hub genes were constructed using the miRNet and NetworkAnalyst tool, and possible key miRNAs and TFs were predicted. Finally, receiver operating characteristic curve (ROC) analysis was used to validate the hub genes. A total of 958 DEGs, including 479 up regulated genes and 479 down regulated genes, were screened between endometriosis and normal control samples. GO and REACTOME pathway enrichment analyses of the 958 DEGs showed that they were mainly involved in multicellular organismal process, developmental process, signaling by GPCR and muscle contraction. Further analysis of the PPI network and modules identified 10 hub genes, including VCAM1, SNCA, PRKCB, ADRB2, FOXQ1, MDFI, ACTBL2, PRKD1, DAPK1 and ACTC1. Possible target miRNAs, including hsa-mir-3143 and hsa-mir-2110, and target TFs, including TCF3 and CLOCK, were predicted by constructing a miRNA-hub gene regulatory network and TF-hub gene regulatory network. This investigation used bioinformatics techniques to explore the potential and novel biomarkers. These biomarkers might provide new ideas and methods for the early diagnosis, treatment, and monitoring of endometriosis.

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RGS7 balances acetylation/de-acetylation of p65 to control chemotherapy-dependent cardiac inflammation

Cited by 3 publications

References 87 publications

RGS6 drives cardiomyocyte death following nucleolar stress by suppressing Nucleolin/miRNA-21

RGS6 drives cardiomyocyte death following nucleolar stress by suppressing Nucleolin/miRNA-21

Role of Histone Modifications in Kidney Fibrosis

Screening and identification of key biomarkers associated with endometriosis using bioinformatics and next generation sequencing data analysis

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