|
|
Advance of connexin 43 and connexin 43-formed channels in the spinal cord injury |
ZHANG Shuangshuang HU Ji▲ HUANG Jinxiu XIE Lijie LIU Jiao |
Department of Anesthesiology, Liyuan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Hubei Province, Wuhan 430077, China |
|
|
Abstract Connexin 43 are integral membrane proteins which span the plasma membrane four times, and widely distributed in the central nervous system. Connexin 43 can form hemi channels and gap junctions which provides a direct cytoplasmic pathway between contacting cells. In the spinal cord injury, the levels of connexin 43 mRNA and protein obviously up-regulated. Also, the permeability of the hemichannels and gap junctions increased, which form a well-known pathway for the release of intracellularmetabolites and the entry of extracellularsubstances, that can play major roles in the secondary injury by the way of aggravating the inflammatory response, disruption of blood-spinal cord barrier, and neuronal death. In addition, the blockers of connexin 43 channels and other methods which regulate the expression of connexin 43 and the permeability of connexin 43 channels can act obvious protective effects in the spinal cord injury. This review discusses the latent injury mechanisms induced by connexin 43 and connexin 43 channels in the spinal cord injury, and relevant treatments on the basis of it.
|
|
|
|
|
[1] Singh A,Tetreault L,Kalsi-Ryan S,et al. Global prevalence and incidence of traumatic spinal cord injury [J]. Clin Epidemiol,2014,6:309-331.
[2] Khaing ZZ,Ehsanipour A,Hofstetter CP,et al.Injectable hydrogels for spinalcord repair: afocus on swellingand intraspinal pressure [J]. Cells Tissues Organs,2015,202(1-2):67-84.
[3] Schulz R,Gorge PM,Gorge A,et al. Connexin 43 is an emerging therapeutic target in ischemia/reperfusion injury, cardioprotection and neuroprotection [J]. Pharmacol Therapeut,2015,153:90-106.
[4] Saez JC,Berthoud VM,Branes MC,et al. Plasma membrane channels formed by connexins: their regulation and functions [J]. Physiol Rev,2003,83(4):1359 -1400.
[5] Orellana JA,Saez PJ,Shoji KF,et al. Modulation of brain hemichannels and gap junction channels by pro-inflammatory agents and their possible role in neurodegeneration [J]. Antioxid Redox Sign,2009,11(2):369-399.
[6] Dunn CA,Su V,Lau AF,et al. Activation of Akt,not connexin 43 protein ubiquitination,regulates gap junction stability [J]. J Biol Chem,2012,287(4):2600-2607.
[7] Schulz R,Heusch G. Connexin 43 and ischemic preconditioning [J]. Cardiovasc Res,2004,62(2):335-344.
[8] Lee IH,Lindqvist E,Kiehn O,et al. Glial and neuronal connexin expression patterns in the rat spinal cord during development and following injury [J]. J Comp Neurol,2005, 489(1):1–10.
[9] Cronin M,Anderson PN,Cook JE,et al. Blocking connexin43 expression reduces inflammation and improves functional recovery after spinal cord injury [J]. Mol Cell Neurosci,2008,39(2):152–160.
[10] O′Carroll SJ,Gorrie CA,Velamoor S,et al. Connexin43 mimetic peptide is neuroprotective and improves function following spinal cord injury [J]. J Neurosci Res,2013,75(3):256–267.
[11] O′Carroll SJ,Alkadhi M,Nicholson LF,et al. Connexin43 mimetic peptides reduce swelling,astrogliosis, and neuronal cell death after spinalcord injury [J]. Cell Commun Adhes,2008,15(1):27–42.
[12] Yang L,Jones NR,Blumbergs PC,et al. Severity-dependent expression of pro-inflammatory cytokines in traumatic spinal cord injury in the rat [J]. J Clin Neurosci,2005,12(3):276–284.
[13] Taoka Y,Okajima K. Role of leukocytes in spinal cord injury in rats [J]. J Neurotrauma,2000,17(3):219–229.
[14] Sumi Y,Woehrle T,Chen Y,et al. Plasma ATP is required forneutrophil activation in a mouse sepsis model [J]. Shock,2014,42(2): 142-147.
[15] Ballabh P,Braun A,Nedergaard M. The blood–brain barrier: an overview: structure, regulation, and clinical implications [J]. Neurobiol Dis,2004,16(1):1-13.
[16] Fang B,Li XM,SunXJ,et al. Ischemic preconditioning protects against spinal cordischemia-reperfusion injury in rabbits by attenuatingblood spinal cord barrier disruption [J]. J Mol Sci,2013,14(5):10343-10354.
[17] Taoka YJ,Okajima K. Spinal cord injury in the rat [J]. Prog Neurobiol,1998,56(3):341-358.
[18] De Bock M,Wang N,Decrock E,et al.Intracellular cleavage of the Cx43 C-Terminal domain bymatrix-metalloproteases: anovel contributor to inflammation? [J]. Mediat Inflamm,2015,2015:257471.
[19] Eugenin EA,Branes MC,Berman JW,et al. TNF-αPlus IFN-γinduce connexin43 expression andformation of gap junctions between human monocytes/macrophages that enhance physiologicalresponses [J]. J Immunol,2003,170(3):1320-1328.
[20] Kolomytkin OV,Marino AA,Waddell DD,et al. IL-1-βinduced production of metalloproteinases by synovial cells depends on gap junction conductance [J]. Am J Physiol Cell Physiol,2002,282(6):1254-1260.
[21] Anderson CM,Swanson RA. Astrocyte glutamate transport: review ofproperties, regulation, and physiological functions [J]. Glia,2000,32(1):1-14.
[22] Zipfel GJ,Babcock DJ,Lee JM,et al. Neuronal apoptosis after CNS injury: the roles of glutamate and calcium [J]. J Neurotrauma,2000,17(10):857-869.
[23] Abudara V,Roux L,Dallerac G,et al. Activated microglia impairs neuroglial interaction by opening Cx43 hemichannels in hippocampal astrocytes [J]. Glia,2015,63(5):795-811.
[24] Orellana JA,Froger N,Ezan P,et al. ATP and glutamate released via astroglial connexin43 hemichannels mediate neuronal death through activation of pannexin 1 hemichannels [J]. J Neurochem,2011,118(5):826-840.
[25] Orellana JA,Shoji KF,Abudara V,et al. Amyloid β-induced death in neurons involves glial and neuronal hemichannels [J]. J Neurosci,2011,31(13):4962-4977.
[26] Mungrue IN,Bredt DS. nNOS at a glance: implications for brain and brawn [J]. J Cell Sci,2004,117(13):2627-2629.
[27] Bodendiek SB,Raman G. Connexin modulators and their potential targets under the magnifying glass [J]. Curr Med Chem,2010,17(34):4191-4230.
[28] Evans WH,Boitano S. Connexin mimetic peptides: specific inhibitors of gap- junctional intercellular communication [J]. Biochem Soc Trans,2001,29(4):606-612.
[29] Warner A,Clements DK,Parikh S,et al. Speci fic motifs in the external loops of connexin proteins can determine gap junction formation between chick heart myocytes [J]. J Physiol,1995,488(3):721-728.
[30] Braet K,Vandamme W,Martin PE,et al. Photoliberatinginositol-1,4,5-trisphosphate triggers ATP release that is blocked by the connexin mimetic peptide gap 26 [J]. Cell Calcium,2003,33(1):37-48.
[31] Yoon JJ,Green CR,O′Carroll SJ,et al. Dose-dependent protective effect of connexin43 mimetic peptide against neurodegeneration in an ex vivo model of epileptiform lesion [J]. Epilepsy Res,2010,92(2-3):153-162.
[32] Haapanen H,Heraj?覿rvi J,Arvola O,et al. Remote ischemic preconditioning protects the spinal cord against ischemic insult: an experimental study in a pocrin model [J]. J Thorac Cardiovasc Surg,2015,151(3):777-785.
[33] Candilio L,Malik A,Hausenloy DJ. Protection of organs other than the heart by remote ischemic conditioning [J]. J Cardiovasc Med,2013,14(3):193-205.
[34] Brandenburger T,Huhn R,Galas A,et al. Remote ischemic preconditioning preserves Connexin 43 phosphorylation in the rat heart in vivo [J]. J Transl Med,2014,12:228.
[35] Haapanen H,Heraj?覿rvi J,Arvola O,et al. Remote ischemic preconditioning protects the spinal cord against ischemic insult: an experimental study in a pocrin model [J]. J Thorac Cardiovasc Surg,2015,151(3):777-785.
[36] Candilio L,Malik A,Hausenloy DJ. Protection of organs other than the heart by remote ischemic conditioning [J]. J Cardiovasc Med,2013,14(3):193-205. |
|
|
|