BACKGROUND Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination.Conversely,reduced expression result...BACKGROUND Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination.Conversely,reduced expression results in a loss of this capacity to facilitate cyclin E degradation.The ubiquitination and degradation of cyclin E1 may be associated with phosphorylation at specific sites on the protein,with Cx43 potentially enhancing this process by facilitating the phosphorylation of these critical residues.AIM To investigate the correlation between expression of Cx43,SKP1/Cullin1/F-box(SCF)FBXW7,p-cyclin E1(ser73,thr77,thr395)and clinicopathological indexes in colon cancer.METHODS Expression levels of Cx43,SCF^(FBXW7),p-cyclin E1(ser73,thr77,thr395)in 38 clinical colon cancer samples were detected by immunohistochemistry and were analyzed by statistical methods to discuss their correlations.RESULTS Positive rate of Cx43,SCF^(FBXW7),p-cyclin E1(Ser73),p-cyclin E1(Thr77)and p-cyclin E1(Thr395)in detected samples were 76.32%,76.32%,65.79%,5.26%and 55.26%respectively.Positive expressions of these proteins were not related to the tissue type,degree of tissue differentiation or lymph node metastasis.Cx43 and SCF^(FBXW7)(r=0.749),p-cyclin E1(Ser73)(r=0.667)and p-cyclin E1(Thr395)(r=0.457),SCF^(FBXW7) and p-cyclin E1(Ser73)(r=0.703)and p-cyclin E1(Thr395)(0.415)were correlated in colon cancer(P<0.05),and expressions of the above proteins were positively correlated in colon cancer.CONCLUSION Cx43 may facilitate the phosphorylation of cyclin E1 at the Ser73 and Thr195 sites through its interaction with SCF^(FBXW7),thereby influencing the ubiquitination and degradation of cyclin E1.展开更多
目的观察κ阿片受体选择性激动剂(U50488H)及β肾上腺素受体激动剂(异丙肾上腺素,ISO)对大鼠心脏缺血/再灌注(ischemia and reperfusion,I/R)引起的心律失常的影响,初步探讨U50488H对心肌细胞缝隙连接蛋白Cx43的调节机制。方法实验大鼠...目的观察κ阿片受体选择性激动剂(U50488H)及β肾上腺素受体激动剂(异丙肾上腺素,ISO)对大鼠心脏缺血/再灌注(ischemia and reperfusion,I/R)引起的心律失常的影响,初步探讨U50488H对心肌细胞缝隙连接蛋白Cx43的调节机制。方法实验大鼠随机分为5组即对照组、I/R组、ISO+I/R组、U50488H+ISO+I/R组、Nor-BNI(κ阿片受体阻断剂)+U50488H+ISO+I/R组。观察每组心律失常的发生情况并计算心律失常评分,RT-PCR检测Cx43 mRNA表达及用免疫组化方法显示大鼠心肌Cx43的分布特征,半定量统计分析。结果①心律失常评分:ISO+I/R组高于I/R组(P<0.05),在ISO前给予U50488H则可以降低ISO引起的心律失常(P<0.05),其效应可被Nor-BNI阻断。②Cx43 mRNA水平:ISO+I/R组比I/R组略增高,在ISO前给予U50488H则可使基因表达水平降低(P<0.05),其效应可被Nor-BNI阻断。③Cx43蛋白表达:ISO+I/R组Total-Cx43高于I/R组(P<0.05),P-Cx43降低但与I/R组比较差异无统计学意义,给予U50488H后,可提高总Cx43和P-Cx43表达量(P<0.05),其效应可被Nor-BNI阻断。结论κ阿片受体激动剂可通过抑制β肾上腺素受体对Cx43调节从而发挥抗缺血/再灌注性心律失常的作用。展开更多
基金Supported by Innovative Practice Platform for Undergraduate Students,School of Public Health Xiamen University,No.2021001.
文摘BACKGROUND Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination.Conversely,reduced expression results in a loss of this capacity to facilitate cyclin E degradation.The ubiquitination and degradation of cyclin E1 may be associated with phosphorylation at specific sites on the protein,with Cx43 potentially enhancing this process by facilitating the phosphorylation of these critical residues.AIM To investigate the correlation between expression of Cx43,SKP1/Cullin1/F-box(SCF)FBXW7,p-cyclin E1(ser73,thr77,thr395)and clinicopathological indexes in colon cancer.METHODS Expression levels of Cx43,SCF^(FBXW7),p-cyclin E1(ser73,thr77,thr395)in 38 clinical colon cancer samples were detected by immunohistochemistry and were analyzed by statistical methods to discuss their correlations.RESULTS Positive rate of Cx43,SCF^(FBXW7),p-cyclin E1(Ser73),p-cyclin E1(Thr77)and p-cyclin E1(Thr395)in detected samples were 76.32%,76.32%,65.79%,5.26%and 55.26%respectively.Positive expressions of these proteins were not related to the tissue type,degree of tissue differentiation or lymph node metastasis.Cx43 and SCF^(FBXW7)(r=0.749),p-cyclin E1(Ser73)(r=0.667)and p-cyclin E1(Thr395)(r=0.457),SCF^(FBXW7) and p-cyclin E1(Ser73)(r=0.703)and p-cyclin E1(Thr395)(0.415)were correlated in colon cancer(P<0.05),and expressions of the above proteins were positively correlated in colon cancer.CONCLUSION Cx43 may facilitate the phosphorylation of cyclin E1 at the Ser73 and Thr195 sites through its interaction with SCF^(FBXW7),thereby influencing the ubiquitination and degradation of cyclin E1.
文摘目的观察κ阿片受体选择性激动剂(U50488H)及β肾上腺素受体激动剂(异丙肾上腺素,ISO)对大鼠心脏缺血/再灌注(ischemia and reperfusion,I/R)引起的心律失常的影响,初步探讨U50488H对心肌细胞缝隙连接蛋白Cx43的调节机制。方法实验大鼠随机分为5组即对照组、I/R组、ISO+I/R组、U50488H+ISO+I/R组、Nor-BNI(κ阿片受体阻断剂)+U50488H+ISO+I/R组。观察每组心律失常的发生情况并计算心律失常评分,RT-PCR检测Cx43 mRNA表达及用免疫组化方法显示大鼠心肌Cx43的分布特征,半定量统计分析。结果①心律失常评分:ISO+I/R组高于I/R组(P<0.05),在ISO前给予U50488H则可以降低ISO引起的心律失常(P<0.05),其效应可被Nor-BNI阻断。②Cx43 mRNA水平:ISO+I/R组比I/R组略增高,在ISO前给予U50488H则可使基因表达水平降低(P<0.05),其效应可被Nor-BNI阻断。③Cx43蛋白表达:ISO+I/R组Total-Cx43高于I/R组(P<0.05),P-Cx43降低但与I/R组比较差异无统计学意义,给予U50488H后,可提高总Cx43和P-Cx43表达量(P<0.05),其效应可被Nor-BNI阻断。结论κ阿片受体激动剂可通过抑制β肾上腺素受体对Cx43调节从而发挥抗缺血/再灌注性心律失常的作用。
