Maslaňáková Mária, Balogová Lucia, Miškovský Pavol, Tkáčová Ružena, Štroffeková Katarína
Department of Biophysics, Faculty of Natural Sciences, PJ Safarik University, Jesenna 5, Kosice, Slovakia.
Center of Interdisciplinary Biosciences, Faculty of Natural Sciences, PJ Safarik University, Kosice, Slovakia.
Cell Biochem Biophys. 2016 Sep;74(3):435-47. doi: 10.1007/s12013-016-0740-y. Epub 2016 Jun 17.
Understanding apoptosis regulatory mechanisms in endothelial cells (ECs) has great importance for the development of novel therapy strategies for cancer and cardiovascular pathologies. An oxidative stress with the generation of reactive oxygen species (ROS) is a common mechanism causing ECs' dysfunction and apoptosis. The generation of ROS can be triggered by various stimuli including photodynamic therapy (PDT). In most PDT treatments, photosensitizer (PS) is administered systemically, and thus, possibility of high exposure to PS in the ECs remains high. PS accumulation in ECs may be clinically relevant even without PDT, if PS molecules affect the pro-apoptotic cascade without illumination. In the present work, we focused on Hypericin (Hyp) and HypPDT effects on the cell viability, oxidative stress, and the distribution of Bcl2 family members in human coronary artery endothelial (HCAEC) cells. Our findings show that the presence of Hyp itself has an effect on cell viability, oxidative stress, and the distribution of Bcl2 family members, without affecting the mitochondria function. In contrast, HypPDT resulted in mitochondria dysfunction, further increase of oxidative stress and effect on the distribution of Bcl2 family members, and in primarily necrotic type of death in HCAEC cells.
了解内皮细胞（ECs）中的凋亡调控机制对于开发针对癌症和心血管疾病的新型治疗策略具有重要意义。活性氧（ROS）生成所导致的氧化应激是引起ECs功能障碍和凋亡的常见机制。ROS的生成可由包括光动力疗法（PDT）在内的各种刺激触发。在大多数PDT治疗中，光敏剂（PS）是全身给药，因此，ECs中PS高暴露的可能性仍然很高。如果PS分子在无光照的情况下影响促凋亡级联反应，即使没有PDT，PS在ECs中的积累也可能具有临床相关性。在本研究中，我们聚焦于金丝桃素（Hyp）和HypPDT对人冠状动脉内皮（HCAEC）细胞活力、氧化应激以及Bcl2家族成员分布的影响。我们的研究结果表明，Hyp本身的存在对细胞活力、氧化应激以及Bcl2家族成员的分布有影响，但不影响线粒体功能。相反，HypPDT导致线粒体功能障碍，氧化应激进一步增加，并影响Bcl2家族成员的分布，且主要导致HCAEC细胞发生坏死型死亡。
