1. Using SEA0400, a potent and selective inhibitor of the Na+-Ca2+ exchanger (NCX), we examined whether NCX is involved in nitric oxide (NO)-induced disturbance of endoplasmic reticulum (ER) Ca2+ homeostasis followed by apoptosis in cultured rat microglia. 2. Sodium nitroprusside (SNP), an NO donor, decreased cell viability in a dose- and time-dependent manner with apoptotic cell death in cultured microglia. 3. Treatment with SNP decreased the ER Ca2+ levels as evaluated by measuring the increase in cytosolic Ca2+ level induced by exposing cells to thapsigargin, an irreversible inhibitor of ER Ca2+-ATPase. 4. The treatment with SNP also increased mRNA expression of CHOP and GPR78, makers of ER stress. 5. SEA0400 at 0.3-1.0 microM protected microglia against SNP-induced apoptosis. 6. SEA0400 blocked not only the SNP-induced decrease in ER Ca2+ levels but also SNP-induced increase in CHOP and GRP78 mRNAs. 7. SEA0400 did not affect capacitative Ca2+ entry in the presence and absence of SNP. 8. SNP increased Na+-dependent 45Ca2+ uptake and this increase was blocked by SEA0400. 9. These results suggest that SNP induces apoptosis via the ER stress pathway and SEA0400 attenuates SNP-induced apoptosis via suppression of the ER stress in cultured microglia. Our findings imply that NCX plays a role in ER Ca2+ depletion under pathological conditions.
1 . Using SEA0400 , a potent and selective inhibitor of the Na+-Ca2 + exchanger ( NCX ) , we examined whether NCX is involved in nitric oxide ( NO)-induced disturbance of endoplasmic reticulum ( ER ) Ca2 + homeostasis followed by apoptosis in cultured rat microglia . 2 . Sodium nitroprusside ( SNP ) , an NO donor , decreased cell viability in a dose- and time - dependent manner with apoptotic cell death in cultured microglia . 3 . Treatment with SNP decreased the ER Ca2 + levels as evaluated by measuring the increase in cytosolic Ca2 + level induced by exposing cells to thapsigargin , an irreversible inhibitor of ER Ca2 + -ATPase . 4 . The treatment with SNP also increased mRNA expression of CHOP and GPR78 , makers of ER stress . 5 . SEA0400 at 0.3 - 1.0 microM protected microglia against SNP - induced apoptosis . 6 . SEA0400 blocked not only the SNP - induced decrease in ER Ca2 + levels but also SNP - induced increase in CHOP and GRP78 mRNAs . 7 . SEA0400 did not affect capacitative Ca2 + entry in the presence and absence of SNP . 8 . SNP increased Na+-dependent 45Ca2 + uptake and this increase was blocked by SEA0400 . 9 . These results suggest that SNP induces apoptosis via the ER stress pathway and SEA0400 attenuates SNP - induced apoptosis via suppression of the ER stress in cultured microglia . Our findings imply that NCX plays a role in ER Ca2 + depletion under pathological conditions .
The small molecule SEA0400 is an inhibitor of which ion antiporter/exchanger?
The small molecule SEA0400 is an inhibitor of which ion antiporter / exchanger ?
NCX
Na(+)/Ca(2+) exchanger NCX