title: CISD2 serves a novel role as a suppressor of nitric oxide signalling and curcumin increases CISD2 expression in spinal cord injuries.
abstract: BACKGROUND
  CISD2 is known to have roles in calcium metabolism, anti-apoptosis, and longevity. However, whether CISD2 is involved in the inflammatory response associated with injuries of the central nervous system (CNS) remains unclear. This issue is particularly relevant for traumatic spinal cord injuries (SCIs), which lack therapeutic targeting and often cause long-term disability in patients. The authors previously demonstrated the neuroprotective effects of curcumin against RANTES-mediated neuroinflammation. In this study, we investigated (1) the role of CISD2 in injury-induced inflammation and (2) whether curcumin influences CISD2 expression in acute SCI.
  
  
  METHODS
  The efficacy of curcumin treatment (40 mg/kg i.p.) was evaluated in an animal model of SCI. In a neural cell culture model, lipopolysaccharide (LPS) was administrated to induce inflammation with the aim of mimicking the situation commonly encountered in SCI. Additionally, knockdown of CISD2 expression by siRNA (siCISD2) in LPS-challenged neural cells was performed to verify the causal relationship between CISD2 and SCI-related inflammation.
  
  
  RESULTS
  The injuries were shown to reduce CISD2 mRNA and protein expression in vivo, and CISD2-positive cells were upregulated by the curcumin treatment. LPS led to a decrease in CISD2 expression in vitro; however, treatment with 1 μM curcumin attenuated the downregulation of CISD2. Furthermore, in a cellular model of LPS-induced injury, the loss of CISD2 function caused by siCISD2 resulted in a pronounced iNOS increase as well as a decrease in BCL2 expression.
  
  
  CONCLUSIONS
  To the best of our knowledge, this is the first study to report the following: (1) CISD2 exerts anti-apoptotic and anti-inflammatory effects in neural cells; and (2) curcumin can attenuate the downregulation of CISD2 in SCI and LPS-treated astrocytes.
authors.affiliation: Department of Biotechnology and Animal Science, College of Bioresources, National Ilan University, Yilan, Taiwan.
authors.forename: Chai-Ching
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Department of Biotechnology and Animal Science, College of Bioresources, National Ilan University, Yilan, Taiwan.
authors.forename: Tien-Huang
authors.initials: TH
authors.lastname: Chiang
authors.affiliation: Department of Biotechnology and Animal Science, College of Bioresources, National Ilan University, Yilan, Taiwan.
authors.forename: Wei-Jung
authors.initials: WJ
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Yu-Yo
authors.initials: YY
authors.lastname: Sun
authors.affiliation: Department and Institute of Physiology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yi-Hsuan
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery, Taipei City Hospital, Zhong Xiao Branch, Taipei, Taiwan; Department of Surgery, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Biotechnology and Animal Science, College of Bioresources, National Ilan University, Yilan, Taiwan. Electronic address: neurosurgery2005@yahoo.com.tw.
authors.forename: Muh-Shi
authors.initials: MS
authors.lastname: Lin
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000187:drug effects / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology*; D004195:Disease Models, Animal; D007249:Inflammation / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013119:Spinal Cord Injuries / Q000473:pathology*
chemical_list: D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C515811:Noxp70 protein, mouse; D009569:Nitric Oxide; D003474:Curcumin
keywords: CISD2; Curcumin; Neuroinflammation; Neuroprotection; Spinal cord injury