Student Research: Kathleen Newhouse

MS, , 2003
Faculty Advisor: Zhengui Xia

MAP Kinase Signaling Mechanisms of Rotenone-induced Toxicity in Human Dopaminergic SH-SY5Y Cells


Abstract

Rotenone is a naturally derived pesticide that has recently been shown to evoke the behavioral and biochemical symptoms of Parkinson's Disease in animal models. though rotenone is known to be an inhibitor of complex I of the mitochondrial electron transport chain, little is known about downstream pathways leading to its toxicity. I have chosen to use human dopaminergic SH-SY5Y cells to study rotenone induced cell death. My studies show that rotenone can induce apoptosis in a model cell culture system. Through western blot analysis, I have found that the c-Jun N terminal protien Kinase (JNK) pathway and the p38 kinase pathway are strongly, though transiently activated by rotenone treatment. JNK and p38 are stress stimulated mitogen activated protien (MAP) kinases which can mediate a variety of cellular responses, including apoptosis. By transiently transfecting plasmids that interfere with the JNK or p38 pathways, I have been able to attenuate rotenone-induced cell death and thus have implicated both pathways in rotenone-induced apoptosis. These studies help provide insights concerning the role of pesticides in neurodegeneration and novel information concerning the molecular mechanisms of rotenone-induced apoptosis in dopaminergic neuronal cells.