Cell-specific Regulation of DJ-1 Protein upon Mouse Hepatitis Virus Infection

Antony, Gisha Rose (2016) Cell-specific Regulation of DJ-1 Protein upon Mouse Hepatitis Virus Infection. Masters thesis, Indian Institute of Science Education& Research Kolkata.

PDF (MS dissertation of Gisha Rose Antony (11MS025)) MS_Thesis_Gisha11025_29-04-2016.pdf - Submitted Version Restricted to Repository staff only Download (2MB)

Abstract

Mouse Hepatitis Virus (MHV) infection in mice causes meningoencephalitis, myelitis, demyelination and axonal loss which mimic certain pathology of human demyelinating disease Multiple Sclerosis (MS). MS is a progressive, neuroinflammatory, demyelinating disease. Neurotropic strain of MHV directly infects neurons and glial cells which could be the probable mechanism behind myelin loss and neurodegeneration. Microglia mediates myelin stripping from the axon during chronic stage of the disease. However the exact mechanism behind microglial activation upon viral infection still needs to be elucidated. One possible mechanism of glial cell activation is the induction of oxidative stress by the generation of Reactive Oxygen Species (ROS). One of the key players in oxidative stress response is the ROS- quencher protein DJ-1. DJ-1 has multifunctional roles in combating oxidative stress; one such functions is the induction of the expression of several anti-oxidant genes. However, role of DJ-1 protein in virus induced neural cell death is not well explored. To investigate this we have tried to find whether there is any change in ROS level upon viral infection in Neuroblastoma (Neuro2A: Neuro2A) and microglial (N9) cell lines. Also we investigated whether it can be correlated with the level of DJ-1 protein. In our study we have shown that upon viral infection, ROS level is increased with a subsequent upregulation of DJ-1 in N9 cells. However no considerable changes in ROS as well as DJ-1 mRNA and protein level were observed in Neuro2A cell lines. With this data we would like to validate whether the role of DJ-1 in oxidative stress is specific for N9 cell line. We would also like to look into the detailed mechanism deciphering the role of DJ-1 in oxidative stress mediated demyelination and axonal loss. Finding of these studies will have long term implication in designing DNA based vaccines using DJ-1 as neuroprotective agent.

Actions (login required)

View Item