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| Proteomics analysis of diacetylmorphine-induced rhythm abnormalities in cardiac muscle cells interfered with by the inhibitor KN-93 |
| JI Min1 SU Liping2 LIU Li2 GUAN Yalin1 XIAO Jinling1 PU Hongwei3 |
1.College of Basic Medical Sciences, Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830011, China;
2.Department of Pathology, the First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830054, China; 3.Department of Discipline Construction, the First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830054, China
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Abstract Objective To analysis the role of the inhibitor KN-93 to intervene in diacetylmorphine-induced rhythm abnormalities in cardiac muscle cells. Methods Myocardial tissue was extracted from 60 SPF-grade SD rats, regardless of male or female. Primary myocardial cells of SD rats were cultured in vitro and divided into the control group and the experimental group. The control group was treated with 100 μmol/L diacetylmorphine for 24 h, and the experimental group was treated with 100 μmol/L diacetylmorphine +1 μmol/L KN-93 for 24 h. The TMT relative quantitative protein technique was used to screen out the proteins with significant expression difference between the control group and the experimental group. The screening criteria were: up-regulation of expression ploidy ＞ 1.2-fold or down-regulation of expression ploidy ＜ 0.83-fold and P＜0.05. The main functions, cellular localization, and biological processes involved in differentially expressed proteins were analyzed by GO functional enrichment. The possible metabolic or signaling pathways involved in differentially expressed proteins were analyzed by KEGG pathway enrichment. Protein interaction network was used to analyze the binding or interaction between proteins. Results Compared with the control group, the phosphorylation level of Ca2+/Calmodulin-dependent protein kinaseⅡ (CaMKⅡ) in the experimental group was decreased, and the difference was statistically significant (P＜0.05). A total of 346 differentially expressed proteins were screened by TMT technology, which were mainly involved in the reaction to cytokines and cell response to cytokine stimulation and other processes, and affected molecular functions such as the same protein binding and signal receptor binding, as well as cellular component proteins such as extracellular regions and extracellular regions. It is mainly concentrated in cancer pathway, PI3K-Akt signaling pathway, human papillomavirus infection, Alzheimer disease, and other signaling pathways. The protein interaction network showed that MSH6, NFkB1, and CaMKⅡ might have protein interaction relationship. Compared with the control group, the protein expressions of ADCY7, NFkB1, MSH6, MMP2, MMP9, NQO1, and TXNRD1 in the experimental group were significantly decreased, with statistical significance (P＜0.05). Conclusion CaMKⅡ may regulate cardiomyocyte apoptosis through cancer pathway signaling pathway by regulating the changes of NFkB, MSH6 and other proteins, and participate in the abnormal rhythm of cardiac muscle cells induced by diacetylmorphine
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