論文 - 詳細
| RRC ID | 3600 |
|---|---|
| 著者 | Luke CJ, Pak SC, Askew YS, Naviglia TL, Askew DJ, Nobar SM, Vetica AC, Long OS, Watkins SC, Stolz DB, Barstead RJ, Moulder GL, Brömme D, Silverman GA. |
| タイトル | An intracellular serpin regulates necrosis by inhibiting the induction and sequelae of lysosomal injury. |
| ジャーナル | Cell |
| Abstract |
Extracellular serpins such as antithrombin and alpha1-antitrypsin are the quintessential regulators of proteolytic pathways. In contrast, the biological functions of the intracellular serpins remain obscure. We now report that the C. elegans intracellular serpin, SRP-6, exhibits a prosurvival function by blocking necrosis. Minutes after hypotonic shock, srp-6 null animals underwent a catastrophic series of events culminating in lysosomal disruption, cytoplasmic proteolysis, and death. This newly defined hypo-osmotic stress lethal (Osl) phenotype was dependent upon calpains and lysosomal cysteine peptidases, two in vitro targets of SRP-6. By protecting against both the induction of and the lethal effects from lysosomal injury, SRP-6 also blocked death induced by heat shock, oxidative stress, hypoxia, and cation channel hyperactivity. These findings suggest that multiple noxious stimuli converge upon a peptidase-driven, core stress response pathway that, in the absence of serpin regulation, triggers a lysosomal-dependent necrotic cell death routine. |
| 巻・号 | 130(6) |
| ページ | 1108-19 |
| 公開日 | 2007-9-21 |
| DOI | 10.1016/j.cell.2007.07.013 |
| PII | S0092-8674(07)00906-3 |
| PMID | 17889653 |
| PMC | PMC2128786 |
| MeSH | Animals Caenorhabditis elegans / enzymology Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans / ultrastructure Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Calcium / metabolism Calcium Channels / metabolism Calpain / genetics Calpain / metabolism Cell Hypoxia Cell Size Cysteine Endopeptidases / genetics Cysteine Endopeptidases / metabolism Genotype Hot Temperature Lysosomes / enzymology Lysosomes / metabolism* Lysosomes / ultrastructure Mutation Necrosis Osmotic Pressure Oxidative Stress Phenotype RNA Interference RNA, Small Interfering / metabolism Serpins / genetics Serpins / metabolism* Time Factors |
| IF | 38.637 |
| 引用数 | 105 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL 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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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 13 |
| 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 | |
| 線虫 | tm1994 |