Abstract：
:Necrostatin-1 (Nec-1) is an inhibitor of necroptosis, playing an important role in inhibition of pathological death in the central nervous system (CNS). Our earlier study suggests that Nec-1 protects the injured spinal cord. In this study, we found that Nec-1 reduces the elevated Ca(2+) concentration in mitochondria post-injury and preserves the remarkably decreased mitochondrial membrane potential (MMP) level post-spinal cord injury (SCI). It also increases the generation of adenosine triphosphate (ATP) by promoting the activity of mitochondrial respiratory chain complex I instead of other complexes, which are significantly decreased due to the injury. Nec-1 also inhibits the release of cytochrome c in the mitochondria and protects the spinal cord from mitochondrial swelling post-SCI. Nec-1 promotes mitochondrial biogenesis by up-regulating mitochondrial transcription factor A (Tfam), in accordance with the mtDNA content. It also inhibits the up-regulation of mitochondrial fusion genes Mnf1, Mnf2 within 6h post-injury and adjusts the abnormal expression of mitochondrial fission gene Fis1. All these results indicate the improvement of mitochondrial functions in injured spinal cord after the treatment of Nec-1. This research revealed the mechanisms of functional protection of Nec-1 by mitigating mitochondrial dysfunction post-SCI.
journal_name
Neurosciencejournal_title
Neuroscienceauthors
Wang Y,Wang J,Yang H,Zhou J,Feng X,Wang H,Tao Ydoi
10.1016/j.neuroscience.2014.12.061subject
Has Abstractpub_date
2015-03-19 00:00:00pages
224-32eissn
0306-4522issn
1873-7544pii
S0306-4522(15)00035-4journal_volume
289pub_type
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