Ceramide Channel Formation in Apoptosis in Stroke

细胞凋亡是许多目前缺乏有效治疗方法的疾病的基础，包括中风、心脏病、神经退行性疾病和癌症。对导致细胞凋亡发生的事件的了解有可能提供多种药物来控制细胞凋亡并减轻中风后的损害。该研究建议的广泛、长期目标是在生物物理和分子水平上阐明细胞凋亡过程中线粒体促凋亡因子释放的机制(S)。近期目标是确定在决定细胞凋亡是否进行的事件中线粒体外膜通透性发生变化的机制--主要研究人员发表的相互矛盾的结果强调，需要进行严格控制的实验，以及寻求取得确定结果的实验计划。该研究建议特别关注神经酰胺通道在诱导细胞色素c从线粒体膜间间隙释放到细胞质中的作用。至少将使用三种不同的实验方法，即平面膜技术、脂质体和线粒体悬浮液，以努力获得明确的结果，以促进细胞凋亡领域的研究。包括神经酰胺通道的特征和神经酰胺通道与bcl2家族的促和抗凋亡成员之间的潜在相互作用。

Apoptosis is fundamental to a plethora of diseases for which effective treatments are currently lacking, including stroke, heart disease, neurodegenerative diseases, and cancer. An understanding of the events that occur leading up to the induction of apoptosis has the potential to provide numerous pharmacological agents that could control apoptosis and lessen the damage following stroke. The broad, long-term objectives of the research proposal are to elucidate the mechanism(s) for release of proapoptotic factors from the mitochondria during apoptosis on the biophysical and molecular level The immediate goals are to determine the mechanisms by which the permeability of the mitochondrial outer membrane is changed in the events that determine whether apoptosis will proceed or not- Conflicting results published by leading researchers emphasize the need for carefully controlled experiments and for an experimental plan that seeks to achieve definitive results. The research proposal specifically focuses on the role of ceramide channels in induction of cytochrome c release from the intermembrane space of the mitochondria to the cytoplasm. At least three different experimental approaches will be utilized, namely the planar membrane technique, liposomes, and mitochondrial suspensions, in an effort to obtain definitive results that can further the field of apoptosis. Both characterization of the ceramide channels and the potential interactions between ceramide channels and pro- and anti-apoptotic members of the bcl-2 family is included.