Res. Chem. Intermed.
, Vol. 28, No. 1, pp. 49 –56 (2002)
Reactive oxygen species are involved in lysophosphatidic
acid-induced apoptosis in rat cerebellar granule cells
, TAOTAO WEI
, JINGWU HOU
, GENGSHAN LI
and WENJUAN XIN
Department of Neurology, People’s Hospital, Wuhan University, Wuhan 430060, P. R. China
Department of Molecular and Cellular Biophysics, Institute of Biophysics, Chinese Academy
of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, P. R. China
Received 25 July 2001; accepted 30 October 2001
Abstract—Lysophosphatidic acid (LPA) induced apoptosis in primary rat cerebellar granule cells,
which was characterized morphologically by chromatin condensation and the formation of apoptotic
bodies. With redox-sensitive uorescence probes DCFH-DA and DHR123, the formation of
endogenous reactive oxygen species (ROS) inside cells during the apoptosis process was monitored by
laser confocal scanning microscopy (LCSM). Pretreatment with the antioxidant tetramethylpyrazine
(TMP) could effectively inhibit the formation of endogenous ROS and protect neurons from apoptosis.
The results suggest that ROS might be involved in LPA-induced apoptosis in neurons.
: Lysophosphatidic acid; cerebellar granule cells; apoptosis; reactive oxygen species.
Lysophosphatidic acid (LPA) is a bioactive phospholipid controlling numerous cel-
luar responses through the activation of speci c G-protein coupled transmembrane
receptors. LPA and LPA receptors are enriched in the brain . LPA has multiple
effects on cells of the brain, including LPA-mediated stimulation of neurite retrac-
tion of neuroblastoma and PC12 cells, stimulation of astrocyte proliferation, and
increased permeability of culture brain endothelial cells [2 –5]. The expression of
LPA receptor is developmentally regulated in the brain, and expression is markedly
increased in association with embryonic programmed cell death of cerebral cor-
tex . The increased LPA in the cerebral spinal uid (CSF) following hemorrhagic
brain injury may lead to an increase in glutamate excitotoxicity via effects on astro-
cytes and neurons . Treatment of hippocampal neurons with 10
M LPA results
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