論文 - 詳細
| RRC ID | 1602 |
|---|---|
| 著者 | Tanaka S, Takehashi M, Iida S, Kitajima T, Kamanaka Y, Stedeford T, Banasik M, Ueda K. |
| タイトル | Mitochondrial impairment induced by poly(ADP-ribose) polymerase-1 activation in cortical neurons after oxygen and glucose deprivation. |
| ジャーナル | J Neurochem |
| Abstract |
Neuronal cells injured by ischemia and reperfusion to a certain extent are committed to death in necrotic or apoptotic form. Necrosis is induced by gross ATP depletion or 'energy crisis' of the cell, whereas apoptosis is induced by a mechanism still to be defined in detail. Here, we investigated this mechanism by focusing on a DNA damage-sensor, poly(ADP-ribose) polymerase-1 (PARP-1). A 2-h oxygen and glucose deprivation (OGD) followed by reoxygenation (Reox) induced apoptosis, rather than necrosis, in rat cortical neurons. During the Reox, PARP-1 was much activated and autopoly(ADP-ribosyl)ated, consuming the substrate, NAD+. Induction of apoptosis by OGD/Reox was suppressed by overexpression of Bcl-2, indicating mitochondrial impairment in this induction process. Mitochondrial permeability transition (MPT), or membrane depolarization, and a release of proapoptotic proteins, i.e. cytochrome c, apoptosis-inducing factor and endonuclease G, from mitochondria were observed during the Reox. These apoptotic changes of mitochondria and the nucleus were attenuated by PARP-1 inhibitors, 1,5-dihydroxyisoquinoline and benzamide, and also by small interfering RNA specific for PARP-1. These results indicated that PARP-1 plays a principal role in inducing mitochondrial impairment that ultimately leads to apoptosis of neurons after cerebral ischemia. |
| 巻・号 | 95(1) |
| ページ | 179-90 |
| 公開日 | 2005-10-1 |
| DOI | 10.1111/j.1471-4159.2005.03353.x |
| PII | JNC3353 |
| PMID | 16181422 |
| MeSH | ADP Ribose Transferases / antagonists & inhibitors ADP Ribose Transferases / metabolism* Animals Apoptosis / drug effects Cells, Cultured Cerebral Cortex / drug effects Cerebral Cortex / enzymology* Cerebral Cortex / physiopathology Electrophysiology Enzyme Activation Enzyme Inhibitors / pharmacology Glucose / deficiency* Hypoxia / physiopathology* Intracellular Membranes / metabolism Mitochondria / metabolism* Mitochondrial Proteins / antagonists & inhibitors Mitochondrial Proteins / metabolism NAD / metabolism Neurons / drug effects Neurons / enzymology* Oxygen / pharmacology Poly (ADP-Ribose) Polymerase-1 Poly(ADP-ribose) Polymerases Proto-Oncogene Proteins c-bcl-2 / metabolism RNA, Small Interfering / pharmacology Rats Rats, Wistar |
| IF | 4.066 |
| 引用数 | 42 |
| WOS 分野 | NEUROSCIENCES BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | AxCANCre (RDB01748) |