蛋白激酶C的激活bryostatin-1调节蛋白酶体功能。
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汗TK,纳尔逊TJ
蛋白激酶C的激活bryostatin-1调节蛋白酶体功能。
J细胞生物化学。2018年8月,119 (8):6894 - 6904。doi: 10.1002 / jcb.26887。Epub 2018年4月25日。
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29693282 (在PubMed]
- 文摘
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蛋白酶体活动ubiquitin-proteasome通路起着关键作用的退化和聚合的间隙,氧化,破坏,和错误折叠的蛋白质来控制蛋白质体内平衡或proteostasis。蛋白酶体活性随细胞衰老,衰老和年龄相关的疾病。因此,增强蛋白酶体功能受损的分子生物学和/或药理学干预是一个活跃的研究领域。自然发生的大环内酯Bryostatin-1,激活PKC同功酶(具体来说,t1 -和-)在sub-nanomolar浓度,但会使浓度更高。在这里,我们现在bryostatin-1增加chymotrypsin-like蛋白酶体活性的20年代组装在sub-nanomolar摩尔浓度(0.3 -30海里)。然而,蛋白酶体活性的微摩尔的浓度减少bryostatin-1 (AG08044培养皮肤:P < 0.005;细胞分化SH-SY5Y: P < 0.02)。调制bryostatin-1蛋白酶体功能的研究在六个真皮成纤维细胞原代细胞行开发从新鲜活检取自健康献血者(n = 2)和获得良好的细胞库(n = 4;没有任何疾病)。Bryostatin-1增强培养皮肤成纤维细胞的蛋白酶体活动获得倾斜和新鲜分离的皮肤成纤维细胞皮肤活检sub-nanomolar浓度(P < 0.015)。 Modulation of proteasome function by bryostatin-1 was confirmed in neuron-like differentiated SH-SY5Y cells. Direct additions of bryostatin-1 into cell lysates prepared from neuron-like differentiated SH-SY5Y, Jurkat cells, and cultured skin fibroblasts were unable to increase proteasome activity indicating that bryostatin-1 can only modulate proteasome activity when added to live cell culture systems. Standard PKC inhibitors blocked bryostatin-1 induced proteasome activity modulation suggesting that enhancement of proteasome activity was mediated by PKC modulation.