Poly (ADP-ribose) polymerase plays an important role in intermittent hypoxia-induced cell death in rat cerebellar granule cells
<p>Abstract</p> <p>Background</p> <p>Episodic cessation of airflow during sleep in patients with sleep apnea syndrome results in intermittent hypoxia (IH). Our aim was to investigate the effects of IH on cerebellar granule cells and to identify the mechanism of IH-induc...
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| Format: | Article |
| Language: | English |
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BMC
2012-03-01
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| Series: | Journal of Biomedical Science |
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| Online Access: | http://www.jbiomedsci.com/content/19/1/29 |
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| author | Chiu Sheng-Chun Huang Sung-Ying Tsai Yu-Chieh Chen Shee-Ping Pang Cheng-Yoong Lien Chih-Feng Lin Yu-Jou Yang Kun-Ta |
| author_facet | Chiu Sheng-Chun Huang Sung-Ying Tsai Yu-Chieh Chen Shee-Ping Pang Cheng-Yoong Lien Chih-Feng Lin Yu-Jou Yang Kun-Ta |
| author_sort | Chiu Sheng-Chun |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Episodic cessation of airflow during sleep in patients with sleep apnea syndrome results in intermittent hypoxia (IH). Our aim was to investigate the effects of IH on cerebellar granule cells and to identify the mechanism of IH-induced cell death.</p> <p>Methods</p> <p>Cerebellar granule cells were freshly prepared from neonatal Sprague-Dawley rats. IH was created by culturing the cerebellar granule cells in the incubators with oscillating O<sub>2 </sub>concentration at 20% and 5% every 30 min for 1-4 days. The results of this study are based on image analysis using a confocal microscope and associated software. Cellular oxidative stress increased with increase in IH. In addition, the occurrence of cell death (apoptosis and necrosis) increased as the duration of IH increased, but decreased in the presence of an iron chelator (phenanthroline) or poly (ADP-ribose) polymerase (PARP) inhibitors [3-aminobenzamide (3-AB) and DPQ]. The fluorescence of caspase-3 remained the same regardless of the duration of IH, and Western blots did not detect activation of caspase-3. However, IH increased the ratio of apoptosis-inducing factor (AIF) translocation to the nucleus, while PARP inhibitors (3-AB) reduced this ratio.</p> <p>Results</p> <p>According to our findings, IH increased oxidative stress and subsequently leading to cell death. This effect was at least partially mediated by PARP activation, resulting in ATP depletion, calpain activation leading to AIF translocation to the nucleus.</p> <p>Conclusions</p> <p>We suggest that IH induces cell death in rat primary cerebellar granule cells by stimulating oxidative stress PARP-mediated calpain and AIF activation.</p> |
| first_indexed | 2024-04-13T05:14:38Z |
| format | Article |
| id | doaj.art-68259e25e59e4c6db28b1d87228e6aad |
| institution | Directory Open Access Journal |
| issn | 1021-7770 1423-0127 |
| language | English |
| last_indexed | 2024-04-13T05:14:38Z |
| publishDate | 2012-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Biomedical Science |
| spelling | doaj.art-68259e25e59e4c6db28b1d87228e6aad2022-12-22T03:00:55ZengBMCJournal of Biomedical Science1021-77701423-01272012-03-011912910.1186/1423-0127-19-29Poly (ADP-ribose) polymerase plays an important role in intermittent hypoxia-induced cell death in rat cerebellar granule cellsChiu Sheng-ChunHuang Sung-YingTsai Yu-ChiehChen Shee-PingPang Cheng-YoongLien Chih-FengLin Yu-JouYang Kun-Ta<p>Abstract</p> <p>Background</p> <p>Episodic cessation of airflow during sleep in patients with sleep apnea syndrome results in intermittent hypoxia (IH). Our aim was to investigate the effects of IH on cerebellar granule cells and to identify the mechanism of IH-induced cell death.</p> <p>Methods</p> <p>Cerebellar granule cells were freshly prepared from neonatal Sprague-Dawley rats. IH was created by culturing the cerebellar granule cells in the incubators with oscillating O<sub>2 </sub>concentration at 20% and 5% every 30 min for 1-4 days. The results of this study are based on image analysis using a confocal microscope and associated software. Cellular oxidative stress increased with increase in IH. In addition, the occurrence of cell death (apoptosis and necrosis) increased as the duration of IH increased, but decreased in the presence of an iron chelator (phenanthroline) or poly (ADP-ribose) polymerase (PARP) inhibitors [3-aminobenzamide (3-AB) and DPQ]. The fluorescence of caspase-3 remained the same regardless of the duration of IH, and Western blots did not detect activation of caspase-3. However, IH increased the ratio of apoptosis-inducing factor (AIF) translocation to the nucleus, while PARP inhibitors (3-AB) reduced this ratio.</p> <p>Results</p> <p>According to our findings, IH increased oxidative stress and subsequently leading to cell death. This effect was at least partially mediated by PARP activation, resulting in ATP depletion, calpain activation leading to AIF translocation to the nucleus.</p> <p>Conclusions</p> <p>We suggest that IH induces cell death in rat primary cerebellar granule cells by stimulating oxidative stress PARP-mediated calpain and AIF activation.</p>http://www.jbiomedsci.com/content/19/1/29Intermittent hypoxiaOxidative stressPoly (ADP-ribose) polymeraseCalpainCerebellar granule cell |
| spellingShingle | Chiu Sheng-Chun Huang Sung-Ying Tsai Yu-Chieh Chen Shee-Ping Pang Cheng-Yoong Lien Chih-Feng Lin Yu-Jou Yang Kun-Ta Poly (ADP-ribose) polymerase plays an important role in intermittent hypoxia-induced cell death in rat cerebellar granule cells Journal of Biomedical Science Intermittent hypoxia Oxidative stress Poly (ADP-ribose) polymerase Calpain Cerebellar granule cell |
| title | Poly (ADP-ribose) polymerase plays an important role in intermittent hypoxia-induced cell death in rat cerebellar granule cells |
| title_full | Poly (ADP-ribose) polymerase plays an important role in intermittent hypoxia-induced cell death in rat cerebellar granule cells |
| title_fullStr | Poly (ADP-ribose) polymerase plays an important role in intermittent hypoxia-induced cell death in rat cerebellar granule cells |
| title_full_unstemmed | Poly (ADP-ribose) polymerase plays an important role in intermittent hypoxia-induced cell death in rat cerebellar granule cells |
| title_short | Poly (ADP-ribose) polymerase plays an important role in intermittent hypoxia-induced cell death in rat cerebellar granule cells |
| title_sort | poly adp ribose polymerase plays an important role in intermittent hypoxia induced cell death in rat cerebellar granule cells |
| topic | Intermittent hypoxia Oxidative stress Poly (ADP-ribose) polymerase Calpain Cerebellar granule cell |
| url | http://www.jbiomedsci.com/content/19/1/29 |
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