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Prostaglandins antagonistically control Bax activation during apoptosis

机译:前列腺素拮抗凋亡过程中的Bax激活

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摘要

The Bax protein (Bcl-2-associated X protein) is pivotal for the apoptotic process. Bax, which resides in an inactive form in the cytosol of healthy cells, is activated during the early stages of apoptosis and becomes associated with mitochondria through poorly understood mechanisms. In this study, we show that a family of bioactive lipids, namely prostaglandins, regulates Bax-dependent apoptosis. The prostaglandin E2 (PGE2) or its derivative PGA2 binds to Bax, induces its change of conformation, and thereby triggers apoptosis. A cysteine present in the loop between the two transmembrane α-helices of Bax, Cys126 is critical for its activation. PGD2 inhibits PGE2 binding to Bax and PGE2-induced apoptosis, as well as cell death induced by staurosporine and UV-B in various cell lines. This result is consistent with the fact that apoptosis is accompanied during these treatments by an increase in PGE2. This process is distinct, yet cooperative, from that involving the BH3-only protein Bid. Our results establish that the PGE2/PGD2 balance is involved in a new early mechanism of control in the activation of Bax during apoptosis.
机译:Bax蛋白(Bcl-2相关的X蛋白)对于凋亡过程至关重要。 Bax处于失活状态,存在于健康细胞的细胞质中,在细胞凋亡的早期被激活,并通过不了解的机制与线粒体相关。在这项研究中,我们表明,生物活性脂质,即前列腺素家族,调节Bax依赖性细胞凋亡。前列腺素E2(PGE2)或其衍生物PGA2与Bax结合,诱导其构象变化,从而触发凋亡。在Bax的两个跨膜α螺旋之间的环中存在一个半胱氨酸Cys126,对其激活至关重要。 PGD​​2抑制PGE2结合Bax和PGE2诱导的细胞凋亡,以及星形孢菌素和UV-B在各种细胞系中诱导的细胞死亡。该结果与以下事实相符:在这些治疗过程中,凋亡伴随着PGE 2的增加。该过程与仅涉及BH3的蛋白Bid的过程截然不同,但仍可协同。我们的研究结果表明,PGE2 / PGD2平衡参与了凋亡过程中Bax激活的新的早期控制机制。

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