title: CIBZ, a novel BTB domain-containing protein, is involved in mouse spinal cord injury via mitochondrial pathway independent of p53 gene.
abstract: Spinal cord injury (SCI) induces both primary uncontrollable mechanical injury and secondary controllable degeneration, which further results in the activation of cell death cascades that mediate delayed tissue damage. To alleviate its impairments and seek for an effective remedy, mRNA differential display was used to investigate gene mRNA expression profiling in mice following SCI. A specific Zinc finger and BTB domain-containing protein, CIBZ, was discovered to implicate in the SCI process for the first time. Further researches indicated that CIBZ was extensively distributed in various tissues, and the expression level was highest in muscle, followed by spinal cord, large intestine, kidney, spleen, thymus, lung, cerebrum, stomach, ovary and heart, respectively. After injury, the CIBZ expression decreased dramatically and reached the lowest level at 8 h, but it gradually increased to the maximal level at 7 d. Caspase-3 and C-terminal-binding protein (CtBP), two CIBZ-related proteins, showed similar tendency. Interestingly, p53 expression remained constant in all groups. Via flow cytometry (FCM) analysis, it was found that the cell death rate in SCI group markedly increased and reached the highest value 1 d after surgery and the mitochondrial transmembrane potential (ΔΨm) at 1 d was the lowest in all groups. Taken together, it is suggested that: (i) in the presence of CtBP, CIBZ gene is involved in secondary injury process and trigger the activation of apoptotic caspase-3 and bax genes independent of p53; (ii) abrupt down-regulation of CtBP at 8 h is a sign of mitochondria dysfunction and the onset of cell death; (iii) it could be used as an inhibitor or target drug of caspase-3 gene to improve spinal cord function.
authors.affiliation: College of Life Sciences, Anhui Normal University, Key Laboratory of Biotic Environment and Ecological Safety in Anhui Province, Wuhu, Anhui, China.
authors.forename: Yafei
authors.initials: Y
authors.lastname: Cai
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Shiyong
authors.initials: S
authors.lastname: Yang
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Honglin
authors.initials: H
authors.lastname: Liu
mesh_terms: D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D012097:Repressor Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013119:Spinal Cord Injuries / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C510763:Zbtb38 protein, mouse; D017931:DNA Primers; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein; D053148:Caspase 3