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Identification of MYSM1 as a regulator of DOX-induced cardiotoxicity. A-B. Heatmaps showing the expression profiles of JAMMs family genes in RNA-seq from mouse cardiac tissues (GSE224157, A) and human cardiac tissues (GSE133054, B, HF = heart failure, NHF = non-heart failure). C. HL-1 cells were transfected with overexpressing plasmids of JAMMs family (e.g. oeMYSM1) or empty vector (EV) plasmid before doxorubicin (DOX) treatment (1 µM, 24 h). Cell viability was measured by CCK8 assay (*, vs. EV; #, vs. EV + DOX; # P < 0.05, *** P < 0.001, n = 6). D. Comprehensive analysis combining RNA-seq datasets and functional screening of JAMMs family for identification of MYSM1 as a regulator in DOX-induced cardiotoxicity. E-F. mRNA levels of Mysm1 in DOX-treated HL-1 cells (E) or mouse cardiac tissues (F) were detected by RT-qPCR (n = 8). G-H. Protein levels of MYSM1 in DOX-treated HL-1 cells (G) or mouse cardiac tissues (H) were assessed by western blotting (n = 3). I. Representative immunofluorescence staining for MYSM1 (red), cardiomyocytes marker α-actinin (green), fibroblasts marker vimentin (green), or macrophages marker F4/80 (green) in heart sections from DOX-treated mice. Slides were counterstained with DAPI (blue). Yellow in merged images denotes regions of colocalization. J. mRNA levels of MYSM1 in cardiomyocytes (CMs), fibroblasts (Fbs), macrophages (Macs), and endothelial cells (ECs) were detected by RT-qPCR under DOX injury (n = 8). (ns = no significance, ** P < 0.01, *** P < 0.001)
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Anthracycline antitumor drug doxorubicin (DOX) induces severe cardiotoxicity. Deubiquitinating enzymes (DUBs) are crucial for protein stability and function and play a significant role in cardiac pathophysiology. By comparing RNA sequencing datasets and conducting functional screening, we determined that Myb-like, SWIRM, and MPN domains 1 (MYSM1) i...
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... determine the functions of the JAMMs family in DOX-induced cardiotoxicity, we initially analyzed the expression profiles of the JAMMs family genes by using RNA-seq of mouse heart tissues treated with DOX (GSE224157, Fig. 1A). In this dataset, the mRNA expression of MYSM1 and PRPF8 were elevated in the DOX group compared to the WT group. Similarly, we observed that the mRNA expression of MYSM1, EIF3F, STAMBP, and BRCC3 were elevated in heart failure (HF) group compared to the control normal heart (NHF) group (GSE133054 , Fig. 1B). Next, we overexpressed ...
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... this dataset, the mRNA expression of MYSM1 and PRPF8 were elevated in the DOX group compared to the WT group. Similarly, we observed that the mRNA expression of MYSM1, EIF3F, STAMBP, and BRCC3 were elevated in heart failure (HF) group compared to the control normal heart (NHF) group (GSE133054 , Fig. 1B). Next, we overexpressed JAMMs family genes in HL-1 cells. ...
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... were counterstained with DAPI (blue). Yellow in merged images denotes regions of colocalization. J. mRNA levels of MYSM1 in cardiomyocytes (CMs), fibroblasts (Fbs), macrophages (Macs), and endothelial cells (ECs) were detected by RT-qPCR under DOX injury (n = 8). (ns = no significance, ** P < 0.01, *** P < 0.001) (2024) 22:593 heart tissues (Fig. 1E-F). Similarly, the protein expression of MYSM1 was upregulated in DOX-treated HL-1 cells and mouse heart tissues ( Fig. 1G-H). We further analyzed the expression and cellular distribution of MYSM1 in heart sections through double-immunofluorescence staining. The results revealed that the increase in MYSM1 was primarily localized to and ...
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... in cardiomyocytes (CMs), fibroblasts (Fbs), macrophages (Macs), and endothelial cells (ECs) were detected by RT-qPCR under DOX injury (n = 8). (ns = no significance, ** P < 0.01, *** P < 0.001) (2024) 22:593 heart tissues (Fig. 1E-F). Similarly, the protein expression of MYSM1 was upregulated in DOX-treated HL-1 cells and mouse heart tissues ( Fig. 1G-H). We further analyzed the expression and cellular distribution of MYSM1 in heart sections through double-immunofluorescence staining. The results revealed that the increase in MYSM1 was primarily localized to and elevated in cardiomyocytes (marked with α-actinin), but not in primary fibroblasts (marked with vimentin) or macrophages ...
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... and cellular distribution of MYSM1 in heart sections through double-immunofluorescence staining. The results revealed that the increase in MYSM1 was primarily localized to and elevated in cardiomyocytes (marked with α-actinin), but not in primary fibroblasts (marked with vimentin) or macrophages (marked with F4/80), following DOX treatment ( Fig. 1I and Fig. S1A). This finding was confirmed by examining the MYSM1 expression in cardiomyocytes isolated from DOX-treated mice (Fig. S1B). RT-qPCR further showed that DOX significantly increased the mRNA levels of Mysm1 in cardiomyocytes rather than non-cardiomyocytes (Fig. 1J). These results indicated that cardiomyocyte MYSM1 may serve ...
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... distribution of MYSM1 in heart sections through double-immunofluorescence staining. The results revealed that the increase in MYSM1 was primarily localized to and elevated in cardiomyocytes (marked with α-actinin), but not in primary fibroblasts (marked with vimentin) or macrophages (marked with F4/80), following DOX treatment ( Fig. 1I and Fig. S1A). This finding was confirmed by examining the MYSM1 expression in cardiomyocytes isolated from DOX-treated mice (Fig. S1B). RT-qPCR further showed that DOX significantly increased the mRNA levels of Mysm1 in cardiomyocytes rather than non-cardiomyocytes (Fig. 1J). These results indicated that cardiomyocyte MYSM1 may serve as a ...
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... in MYSM1 was primarily localized to and elevated in cardiomyocytes (marked with α-actinin), but not in primary fibroblasts (marked with vimentin) or macrophages (marked with F4/80), following DOX treatment ( Fig. 1I and Fig. S1A). This finding was confirmed by examining the MYSM1 expression in cardiomyocytes isolated from DOX-treated mice (Fig. S1B). RT-qPCR further showed that DOX significantly increased the mRNA levels of Mysm1 in cardiomyocytes rather than non-cardiomyocytes (Fig. 1J). These results indicated that cardiomyocyte MYSM1 may serve as a potential regulator in DOXinduced ...
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... vimentin) or macrophages (marked with F4/80), following DOX treatment ( Fig. 1I and Fig. S1A). This finding was confirmed by examining the MYSM1 expression in cardiomyocytes isolated from DOX-treated mice (Fig. S1B). RT-qPCR further showed that DOX significantly increased the mRNA levels of Mysm1 in cardiomyocytes rather than non-cardiomyocytes (Fig. 1J). These results indicated that cardiomyocyte MYSM1 may serve as a potential regulator in DOXinduced ...
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... has three main biochemical characteristics, including ROS dependence, accumulation of ferrous iron (Fe 2+ ), and lipid peroxidation [17]. As presented in Fig. 7A, MYSM1 knockdown led to a decrease in Fe 2+ content in DOX injury. Additionally, MYSM1 knockdown diminished the elevated MDA levels induced by DOX (Fig. 7B) and augmented both GSH levels and SOD activity (Fig. 7C-D). Conversely, the upregulation of MYSM1 further augmented DOX-induced the increase in Fe 2+ content (Fig. 7E), elevated the MDA ...
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... Besides cancer, the regulation of ubiquitination on ferroptosis also plays a role in the treatment of other diseases. As a deubiquitinating enzyme, mysm1 regulates trim 21 stability and mediates doxorubicin (DOX) -induced ferroptosis in cardiomyocytes, suggesting that cardiomyocyte specific knockdown of mysm1 may be an attractive therapeutic strategy for this disease (82). The latest research found that Hyperoside, a bioactive compound extracted from traditional Chinese medicine, promotes the translocation of Nrf2 to the nucleus by inhibiting ubiquitin mediated degradation of Nrf2, resulting in the up regulation of the expression of anti ferroptosis genes, and inhibiting ferroptosis in the treatment of sepsis induced acute lung injury (83). ...
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