Caspase-1 inhibitor prevents neurogenic pulmonary edema after subarachnoid hemorrhage in mice
BACKGROUND AND PURPOSE: We examined the effects of a caspase-1 inhibitor, N-Ac-Tyr-Val-Ala-Asp-chloromethyl ketone (Ac-YVAD-CMK), on neurogenic pulmonary edema in the endovascular perforation model of subarachnoid hemorrhage (SAH) in mice.
METHODS: Ninety-seven mice were assigned to sham, SAH+vehicle, SAH+Ac-YVAD-CMK (6 or 10 mg/kg), and SAH+Z-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK, 6 mg/kg) groups. Drugs were intraperitoneally injected 1 hour post-SAH. Pulmonary edema measurements, Western blot for interleukin-1beta, interleukin-18, myeloperoxidase, matrix metalloproteinase (MMP)-2, MMP-9, cleaved caspase-3 and zona occludens-1, MMP zymography, terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining, and immunostaining were performed on the lung at 24 hours post-SAH.
RESULTS: Ten- but not 6-mg/kg of Ac-YVAD-CMK significantly inhibited a post-SAH increase in the activation of interleukin-1beta and caspase-3 and the number of terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling-positive pulmonary endothelial cells, preventing neurogenic pulmonary edema. Another antiapoptotic drug, Z-VAD-FMK, also reduced neurogenic pulmonary edema. SAH did not change interleukin-18, myeloperoxidase, MMP-2, MMP-9, zona occludens-1 levels, or MMP activity.
CONCLUSIONS: We report for the first time that Ac-YVAD-CMK prevents lung cell apoptosis and neurogenic pulmonary edema after SAH in mice.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2009 |
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| Erschienen: |
2009 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:40 |
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| Enthalten in: |
Stroke - 40(2009), 12 vom: 04. Dez., Seite 3872-5 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Suzuki, Hidenori [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.01.2010 Date Revised 20.10.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1161/STROKEAHA.109.566109 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM192479393 |
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| 041 | |a eng | ||
| 100 | 1 | |a Suzuki, Hidenori |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Caspase-1 inhibitor prevents neurogenic pulmonary edema after subarachnoid hemorrhage in mice |
| 264 | 1 | |c 2009 | |
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| 500 | |a Date Completed 12.01.2010 | ||
| 500 | |a Date Revised 20.10.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND AND PURPOSE: We examined the effects of a caspase-1 inhibitor, N-Ac-Tyr-Val-Ala-Asp-chloromethyl ketone (Ac-YVAD-CMK), on neurogenic pulmonary edema in the endovascular perforation model of subarachnoid hemorrhage (SAH) in mice | ||
| 520 | |a METHODS: Ninety-seven mice were assigned to sham, SAH+vehicle, SAH+Ac-YVAD-CMK (6 or 10 mg/kg), and SAH+Z-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK, 6 mg/kg) groups. Drugs were intraperitoneally injected 1 hour post-SAH. Pulmonary edema measurements, Western blot for interleukin-1beta, interleukin-18, myeloperoxidase, matrix metalloproteinase (MMP)-2, MMP-9, cleaved caspase-3 and zona occludens-1, MMP zymography, terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining, and immunostaining were performed on the lung at 24 hours post-SAH | ||
| 520 | |a RESULTS: Ten- but not 6-mg/kg of Ac-YVAD-CMK significantly inhibited a post-SAH increase in the activation of interleukin-1beta and caspase-3 and the number of terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling-positive pulmonary endothelial cells, preventing neurogenic pulmonary edema. Another antiapoptotic drug, Z-VAD-FMK, also reduced neurogenic pulmonary edema. SAH did not change interleukin-18, myeloperoxidase, MMP-2, MMP-9, zona occludens-1 levels, or MMP activity | ||
| 520 | |a CONCLUSIONS: We report for the first time that Ac-YVAD-CMK prevents lung cell apoptosis and neurogenic pulmonary edema after SAH in mice | ||
| 650 | 4 | |a Letter | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 7 | |a Amino Acid Chloromethyl Ketones |2 NLM | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a Caspase Inhibitors |2 NLM | |
| 650 | 7 | |a Cysteine Proteinase Inhibitors |2 NLM | |
| 650 | 7 | |a Interleukin-1beta |2 NLM | |
| 650 | 7 | |a N-acetyl-tyrosyl-valyl-alanyl-aspartyl chloromethyl ketone |2 NLM | |
| 650 | 7 | |a benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone |2 NLM | |
| 650 | 7 | |a Caspase 1 |2 NLM | |
| 650 | 7 | |a EC 3.4.22.36 |2 NLM | |
| 700 | 1 | |a Sozen, Takumi |e verfasserin |4 aut | |
| 700 | 1 | |a Hasegawa, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Wanqiu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, John H |e verfasserin |4 aut | |
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