Department of Biological Sciences, School of Science and Technology, Sunway University, No. 5 Jalan Universiti, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia.
Department of Medical Sciences, School of Healthcare and Medical Sciences, Sunway University, No. 5 Jalan Universiti, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia.
Molecules. 2018 Oct 4;23(10):2537. doi: 10.3390/molecules23102537.
A group of stable, water-soluble and membrane-bound proteins constitute the pore forming toxins (PFTs) in cnidarians. They interact with membranes to physically alter the membrane structure and permeability, resulting in the formation of pores. These lesions on the plasma membrane causes an imbalance of cellular ionic gradients, resulting in swelling of the cell and eventually its rupture. Of all cnidarian PFTs, actinoporins are by far the best studied subgroup with established knowledge of their molecular structure and their mode of pore-forming action. However, the current view of necrotic action by actinoporins may not be the only mechanism that induces cell death since there is increasing evidence showing that pore-forming toxins can induce either necrosis or apoptosis in a cell-type, receptor and dose-dependent manner. In this review, we focus on the response of the cellular immune system to the cnidarian pore-forming toxins and the signaling pathways that might be involved in these cellular responses. Since PFTs represent potential candidates for targeted toxin therapy for the treatment of numerous cancers, we also address the challenge to overcoming the immunogenicity of these toxins when used as therapeutics.
一组稳定的、水溶性的和膜结合的蛋白质构成了刺胞动物中的孔形成毒素（PFTs）。它们与膜相互作用，物理改变膜结构和通透性，导致孔的形成。这些质膜上的损伤导致细胞离子梯度失衡，导致细胞肿胀，最终破裂。在所有刺胞动物的 PFTs 中，肌动蛋白孔形成毒素是迄今为止研究最多的亚群，其分子结构及其成孔作用模式已得到确立。然而，目前对肌动蛋白孔形成毒素引起坏死的作用的看法可能不是诱导细胞死亡的唯一机制，因为越来越多的证据表明，孔形成毒素可以以细胞类型、受体和剂量依赖的方式诱导细胞坏死或凋亡。在这篇综述中，我们重点介绍了细胞免疫系统对刺胞动物孔形成毒素的反应，以及可能参与这些细胞反应的信号通路。由于 PFTs 是针对多种癌症的靶向毒素治疗的潜在候选物，因此我们还解决了在将这些毒素用作治疗剂时克服其免疫原性的挑战。
