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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Int+J+Physiol+Pathophysiol+Pharmacol
2015 ; 7
(2
): 107-14
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Aralar plays a significant role in maintaining the survival and mitochondrial
membrane potential of BV2 microglia
#MMPMID26330901
Wang C
; Zhang J
; Zhang M
; Chen H
; Ying W
Int J Physiol Pathophysiol Pharmacol
2015[]; 7
(2
): 107-14
PMID26330901
show ga
NADH shuttles mediate the transfer of the reducing equivalents of cytosolic NADH
into mitochondria. Increasing evidence has suggested that malate-aspartate
shuttle (MAS), one of the two types of NADH shuttles, plays important roles in
certain biological processes. Aralar/AGC1, a Ca(2+)-dependent aspartate-glutamate
carrier on mitochondrial membrane, is a component of MAS. It has been reported
that Aralar plays crucial roles in linking increased cytosolic Ca(2+)
concentrations to enhanced mitochondrial energy metabolism of neurons under
certain conditions, while the role of the carrier in cell survival remains
unknown. In the current study, we tested our hypothesis that Aralar plays an
important role in cell survival, using BV2 microglia as a cellular model. Our
study showed that Aralar siRNA-produced decrease in the Aralar level led to a
significant reduction of the cell survival. Our FACS-based Annexin V/7-AAD assays
also showed that the Aralar siRNA treatment led to a significant increase in
apoptosis of the cells. Moreover, the Aralar siRNA treatment led to both
mitochondrial depolarization and decreases in the intracellular ATP level of the
cells. Collectively, our study has provided the first evidence suggesting that
Aralar plays a significant role in cell survival, at least for such cell types as
BV2 microglia, possibly by producing mitochondrial depolarization. These
observations have also provided novel information for understanding the roles of
NADH shuttles in cell survival.