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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Osakada, Masakazu Ago, Yukio Baba, Akemichi Matsuda, Toshio Takemura, Motohiko Nagano, Takayuki Koyama, Yutaka Maeda, Sadaaki |
| Description | Author Affiliation: Nagano T ( Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.) |
| Abstract | 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. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 5 |
| Volume Number | 144 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2005-03-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Aniline Compounds Pharmacology Apoptosis Microglia Drug Effects Phenyl Ethers Sodium-Calcium Exchanger Antagonists & Inhibitors Animals CCAAT-Enhancer-Binding Proteins Genetics Metabolism Calcium Cell Survival Cells, Cultured Endoplasmic Reticulum Heat-Shock Proteins Molecular Chaperones Nitric Oxide Donors Nitroprusside RNA, Messenger Rats, Wistar Transcription Factor CHOP Transcription Factors Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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