目的探讨位于非胱硫醚β-合成酶(cystathionineβ-synthase,CBS)区域的PRKAG2基因G100S突变对小鼠心肌细胞单磷酸腺苷活化蛋白激酶(AMPK)活性的影响。方法建立人源PRKAG2(G100S)转基因小鼠模型,分别随机选取N4代4周龄、12周龄的转基因...目的探讨位于非胱硫醚β-合成酶(cystathionineβ-synthase,CBS)区域的PRKAG2基因G100S突变对小鼠心肌细胞单磷酸腺苷活化蛋白激酶(AMPK)活性的影响。方法建立人源PRKAG2(G100S)转基因小鼠模型,分别随机选取N4代4周龄、12周龄的转基因小鼠和同窝野生型小鼠各6只,用磷酸化检测试剂盒检测小鼠心肌细胞中AMPK活性,比较转基因小鼠与同窝野生型小鼠AMPK活性的差异,并观察随着周龄的增长转基因小鼠AMPK活性的变化。结果 4周龄和12周龄的转基因小鼠心肌细胞中AMPK活性均低于同窝野生型小鼠(0.042±0.013 vs 0.063±0.013,0.032±0.008 vs 0.062±0.018),差异均有统计学意义(P=0.019,P=0.004)。12周龄和4周龄的转基因小鼠心肌细胞中AMPK活性差异无统计学意义(P=0.135)。结论 PRKAG2基因G100S突变可导致转基因小鼠心肌细胞AMPK活性下降,而且AMPK活性并不随着转基因小鼠周龄的增长而变化。展开更多
Tangier disease is caused by mutations in ATP binding cassette transporter A1( ABCA1). ABCA1 interacts with lipid-free apolip oproteins, promoting phospholipid and cholesterol efflux from cells and giving r ise to HDL...Tangier disease is caused by mutations in ATP binding cassette transporter A1( ABCA1). ABCA1 interacts with lipid-free apolip oproteins, promoting phospholipid and cholesterol efflux from cells and giving r ise to HDL particles. ABCA1 may act as a phospholipid translocase facilitating p hospholipid binding to apoA-I. ABCA1 gene expression is upregulated in cholester ol-loaded cells as a result of activation of LXR/RXR-mediated gene transcription . LXR and RXR coordinately induce a battery of genes mediating cellular choleste rol efflux, centripetal cholesterol transport, and cholesterol excretion in bile . Small-molecule activators of LXR/RXR or other stimulators of macrophage or int estinal cholesterol efflux hold great promise as future treatments for atheroscl erosis.展开更多
文摘目的探讨位于非胱硫醚β-合成酶(cystathionineβ-synthase,CBS)区域的PRKAG2基因G100S突变对小鼠心肌细胞单磷酸腺苷活化蛋白激酶(AMPK)活性的影响。方法建立人源PRKAG2(G100S)转基因小鼠模型,分别随机选取N4代4周龄、12周龄的转基因小鼠和同窝野生型小鼠各6只,用磷酸化检测试剂盒检测小鼠心肌细胞中AMPK活性,比较转基因小鼠与同窝野生型小鼠AMPK活性的差异,并观察随着周龄的增长转基因小鼠AMPK活性的变化。结果 4周龄和12周龄的转基因小鼠心肌细胞中AMPK活性均低于同窝野生型小鼠(0.042±0.013 vs 0.063±0.013,0.032±0.008 vs 0.062±0.018),差异均有统计学意义(P=0.019,P=0.004)。12周龄和4周龄的转基因小鼠心肌细胞中AMPK活性差异无统计学意义(P=0.135)。结论 PRKAG2基因G100S突变可导致转基因小鼠心肌细胞AMPK活性下降,而且AMPK活性并不随着转基因小鼠周龄的增长而变化。
文摘Tangier disease is caused by mutations in ATP binding cassette transporter A1( ABCA1). ABCA1 interacts with lipid-free apolip oproteins, promoting phospholipid and cholesterol efflux from cells and giving r ise to HDL particles. ABCA1 may act as a phospholipid translocase facilitating p hospholipid binding to apoA-I. ABCA1 gene expression is upregulated in cholester ol-loaded cells as a result of activation of LXR/RXR-mediated gene transcription . LXR and RXR coordinately induce a battery of genes mediating cellular choleste rol efflux, centripetal cholesterol transport, and cholesterol excretion in bile . Small-molecule activators of LXR/RXR or other stimulators of macrophage or int estinal cholesterol efflux hold great promise as future treatments for atheroscl erosis.
