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Experimental research

Minocycline impedes mitochondrial-dependent cell death and stabilizes expression of hypoxia inducible factor-1α in spinal cord injury

Guolei Zhang, Junpu Zha, Junchuan Liu, Jun Di

Arch Med Sci
Online publish date: 2018/02/15
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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.

minocycline, mitochondrial proteins, apoptosis, HIF-1α, spinal cord injury

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