Ceramide Channel Formation in Apoptosis in Stroke

细胞凋亡是目前缺乏有效治疗的多种疾病的基础，包括中风、心脏病、神经退行性疾病和癌症。了解导致细胞凋亡诱导的事件有可能提供许多可以控制细胞凋亡和减轻卒中后损伤的药理学药物。那个女人研究计划的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释放促细胞凋亡因子的机制。近期目标是确定线粒体外膜通透性在决定细胞凋亡是否进行的事件中发生变化的机制-由领先的研究人员发表的验证结果强调需要仔细控制实验和寻求获得明确结果的实验计划。该研究计划特别关注神经酰胺通道在诱导细胞色素c从线粒体膜间隙释放到细胞质中的作用。将利用至少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，以获得明确的结果，可以进一步的细胞凋亡领域。神经酰胺通道的表征和神经酰胺通道与bcl-2家族的促凋亡和抗凋亡成员之间的潜在相互作用都包括在内。

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.