Minocycline impedes mitochondrial-dependent cell death and stabilizes expression of hypoxia inducible factor-1α in spinal cord injury
Introduction One of the crucial mechanisms following spinal cord injury is mitochondria-associated cell death. Minocycline, an anti-inflammatory drug, is well known to impede mitochondrial cell death. However, there has been no study on the effect of minocycline linking Fas cell surface death recept...
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oai:doaj.org-article:2cb86823f2604c689875293b48068ea82021-12-02T18:33:05ZMinocycline impedes mitochondrial-dependent cell death and stabilizes expression of hypoxia inducible factor-1α in spinal cord injury1734-19221896-915110.5114/aoms.2018.73520https://doaj.org/article/2cb86823f2604c689875293b48068ea82019-03-01T00:00:00Zhttps://www.archivesofmedicalscience.com/Minocycline-impedes-mitochondrial-dependent-cell-death-and-stabilizes-expression,81660,0,2.htmlhttps://doaj.org/toc/1734-1922https://doaj.org/toc/1896-9151Introduction One of the crucial mechanisms following spinal cord injury is mitochondria-associated cell death. Minocycline, an anti-inflammatory drug, is well known to impede mitochondrial cell death. However, there has been no study on the effect of minocycline linking Fas cell surface death receptor (FAS)-mediated cell death and hypoxia inducible factor (HIF-1α), the targets involved in mitochondrial cell death. Material and methods Male Sprague Dawley rats (N = 15, divided into three groups) were subjected to traumatic spinal cord injury and were injected with minocycline (n = 5) (90 mg/kg and later a 45 mg/kg dose twice a day (every 12 h)). Injection with sterile PBS in injured animals served as the vehicle (n = 5) and another group comprised healthy animals (n = 5). TUNEL assay was used to quantify cell death. The release of Smac/Diablo, cytochrome-c (cyt-c), HIF-1α, FAS ligand (FASL) and tumour necrosis factor-α (TNF-α) was measured using ELISA. Expression of HIF-1α, FASL and other cell death associated factors was quantified at the mRNA and protein level and confirmed with immunohistochemistry. Results There was a marked reduction in the HIF-1α and FASL expression levels in the minocycline-treated group compared to the vehicle. The reduction of HIF-1α and FASL was associated with other factors linked to cell death (Smac/Diablo, cyt-c, TNF-α, p53, caspase-8 and BH3 interacting domain death agonist (BID)) (p < 0.5; *p < 0.05 vs. vehicle group, **p < 0.01 vs. vehicle group). Conclusions The present study focuses on the investigation of minocycline in inhibiting mitochondria-associated cell death by modulating FASL and HIF-1α expression, which are seemingly interlinked mechanisms contributing to cell death.Guolei ZhangJunpu ZhaJunchuan LiuJun DiTermedia Publishing Housearticleapoptosishif-1αspinal cord injuryminocyclinemitochondrial proteinsapoptosisMedicineRENArchives of Medical Science, Vol 15, Iss 2, Pp 475-483 (2019) |
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DOAJ |
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DOAJ |
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EN |
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apoptosis hif-1α spinal cord injury minocycline mitochondrial proteins apoptosis Medicine R |
| spellingShingle |
apoptosis hif-1α spinal cord injury minocycline mitochondrial proteins apoptosis Medicine R Guolei Zhang Junpu Zha Junchuan Liu Jun Di Minocycline impedes mitochondrial-dependent cell death and stabilizes expression of hypoxia inducible factor-1α in spinal cord injury |
| description |
Introduction
One of the crucial mechanisms following spinal cord injury is mitochondria-associated cell death. Minocycline, an anti-inflammatory drug, is well known to impede mitochondrial cell death. However, there has been no study on the effect of minocycline linking Fas cell surface death receptor (FAS)-mediated cell death and hypoxia inducible factor (HIF-1α), the targets involved in mitochondrial cell death.
Material and methods
Male Sprague Dawley rats (N = 15, divided into three groups) were subjected to traumatic spinal cord injury and were injected with minocycline (n = 5) (90 mg/kg and later a 45 mg/kg dose twice a day (every 12 h)). Injection with sterile PBS in injured animals served as the vehicle (n = 5) and another group comprised healthy animals (n = 5). TUNEL assay was used to quantify cell death. The release of Smac/Diablo, cytochrome-c (cyt-c), HIF-1α, FAS ligand (FASL) and tumour necrosis factor-α (TNF-α) was measured using ELISA. Expression of HIF-1α, FASL and other cell death associated factors was quantified at the mRNA and protein level and confirmed with immunohistochemistry.
Results
There was a marked reduction in the HIF-1α and FASL expression levels in the minocycline-treated group compared to the vehicle. The reduction of HIF-1α and FASL was associated with other factors linked to cell death (Smac/Diablo, cyt-c, TNF-α, p53, caspase-8 and BH3 interacting domain death agonist (BID)) (p < 0.5; *p < 0.05 vs. vehicle group, **p < 0.01 vs. vehicle group).
Conclusions
The present study focuses on the investigation of minocycline in inhibiting mitochondria-associated cell death by modulating FASL and HIF-1α expression, which are seemingly interlinked mechanisms contributing to cell death. |
| format |
article |
| author |
Guolei Zhang Junpu Zha Junchuan Liu Jun Di |
| author_facet |
Guolei Zhang Junpu Zha Junchuan Liu Jun Di |
| author_sort |
Guolei Zhang |
| title |
Minocycline impedes mitochondrial-dependent cell death and stabilizes expression of hypoxia inducible factor-1α in spinal cord injury |
| title_short |
Minocycline impedes mitochondrial-dependent cell death and stabilizes expression of hypoxia inducible factor-1α in spinal cord injury |
| title_full |
Minocycline impedes mitochondrial-dependent cell death and stabilizes expression of hypoxia inducible factor-1α in spinal cord injury |
| title_fullStr |
Minocycline impedes mitochondrial-dependent cell death and stabilizes expression of hypoxia inducible factor-1α in spinal cord injury |
| title_full_unstemmed |
Minocycline impedes mitochondrial-dependent cell death and stabilizes expression of hypoxia inducible factor-1α in spinal cord injury |
| title_sort |
minocycline impedes mitochondrial-dependent cell death and stabilizes expression of hypoxia inducible factor-1α in spinal cord injury |
| publisher |
Termedia Publishing House |
| publishDate |
2019 |
| url |
https://doaj.org/article/2cb86823f2604c689875293b48068ea8 |
| work_keys_str_mv |
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| _version_ |
1718377909113061376 |