The Center for Alternatives to Animal Testing is an academic center affiliated with the Division of Toxicological Sciences in the Department of Environmental Health Sciences of the Johns Hopkins University Bloomberg School of Public Health.

 

Johns Hopkins School of Public Health

Research Grants 1998-1999

Mechanisms of Apoptosis and Anti-Apoptosis

Raphael J. Witorsch, PhD
Virginia Commonwealth University School of Medicine, Richmond, Virginia

Apoptosis (Greek expression for "plant shedding leaves"), also referred to as programmed cell death, is the process by which a cell dies in a regulated and organized fashion. Apoptosis exhibits a stereotypical sequence of changes such as cell shrinkage and ultimately fragmentation of the nucleus into membrane-bound vesicles. Apoptosis is the timely cell death that occurs during embryonic development, tissue re-structuring, and aging, as well as the response to such cytotoxic agents as anticancer drugs (e.g., vinblastine, cis-platin) and free radicals. Numerous disease states reflect apoptosis retardation (e.g., cancer, autoimmune disorders) or acceleration (e.g., AIDS, Alzheimer's and Parkinson's diseases). Several intracellular proteins have been associated with the promotion of apoptosis (e.g. bax, Fas, Fas-L, IKBa, glucocorticoid receptor) while others have been associated with its inhibition (e.g., bc1-2, NFK, STAT5). Witorsch and colleagues are studying the regulation of apoptosis at the cellular level using cultured rat lymphoma cells. A microscopic approach, immunocytochemistry, is used to visualize in individual cells the changes in the above proteins under conditions where apoptosis is promoted (e.g., with glucocorticoid hormone or cytotoxic agents) and inhibited (with the peptide hormone, prolactin). By this approach they hope to gain insight into the cellular mechanisms involved in the control of apoptosis and, hence, a better understanding of cytotoxic mechanisms.