Omega-3 and Omega-6 Fatty Acids Suppress ER- and Oxidative Stress in Cultured Neurons and Neuronal Progenitor Cells from Mice Lacking PPT1

Overview

Journal Neurosci Lett

Specialty Neurology

Date 2010 Jun 22

PMID 20561933

Citations 18

Authors

Sung-Jo Kim

Zhongjian Zhang

Arjun Saha

Chinmoy Sarkar

Zhenwen Zhao

Yan Xu

Anil B Mukherjee

Affiliations

Soon will be listed here.

Abstract

Reactive oxygen species (ROS) damage brain lipids, carbohydrates, proteins, as well as DNA and may contribute to neurodegeneration. We previously reported that ER- and oxidative stress cause neuronal apoptosis in infantile neuronal ceroid lipofuscinosis (INCL), a lethal neurodegenerative storage disease, caused by palmitoyl-protein thioesterase-1 (PPT1) deficiency. Polyunsaturated fatty acids (PUFA) are essential components of cell membrane phospholipids in the brain and excessive ROS may cause oxidative damage of PUFA leading to neuronal death. Using cultured neurons and neuroprogenitor cells from mice lacking Ppt1, which mimic INCL, we demonstrate that Ppt1-deficient neurons and neuroprogenitor cells contain high levels of ROS, which may cause peroxidation of PUFA and render them incapable of providing protection against oxidative stress. We tested whether treatment of these cells with omega-3 or omega-6 PUFA protects the neurons and neuroprogenitor cells from oxidative stress and suppress apoptosis. We report here that both omega-3 and omega-6 fatty acids protect the Ppt1-deficient cells from ER- as well as oxidative stress and suppress apoptosis. Our results suggest that PUFA supplementation may have neuroprotective effects in INCL.

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