title: Necrostatin-1 mitigates mitochondrial dysfunction post-spinal cord injury.
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.
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Soochow University, 188 Shizi St., Suzhou, Jiangsu 215006, China; Department of Orthopedics, Clinical Medical College of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu 225001, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Clinical Medical College of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu 225001, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Soochow University, 188 Shizi St., Suzhou, Jiangsu 215006, China. Electronic address: suzhouspine@163.com.
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Soochow University, 188 Shizi St., Suzhou, Jiangsu 215006, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Orthopedics, Clinical Medical College of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu 225001, China.
authors.forename: X
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Orthopedics, Clinical Medical College of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu 225001, China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Clinical Medical College of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu 225001, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Tao
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D007093:Imidazoles / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D063154:Mitochondrial Dynamics / Q000187:drug effects / Q000502:physiology; D024101:Mitochondrial Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D001678:Organelle Biogenesis; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C503403:Fis1 protein, rat; D007093:Imidazoles; D007211:Indoles; D024101:Mitochondrial Proteins; D018696:Neuroprotective Agents; C489030:Tfam protein, rat; D014157:Transcription Factors; C507699:necrostatin-1; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D002118:Calcium
keywords: functional protection; mitochondria; necroptosis; necrostatin-1; spinal cord injury