Hemopexin induces neuroprotection in the rat subjected to focal cerebral ischemia

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• 作者：Beibei Dong (1)
  Min Cai (1)
  Zongping Fang (1)
  Haidong Wei (1)
  Fangyun Zhu (1)
  Guochao Li (1)
  Hailong Dong (1)
  Lize Xiong (2)
  
• 关键词：Hemopexin ; Cerebral ischemia ; Neuroprotection ; Intracerebroventricular injection ; Endogenous protection
• 刊名：BMC Neuroscience
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：14
• 期：1
• 全文大小：2065KB
• 参考文献：1. Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, Carnethon MR, Dai S, De Simone G, Ford ES, / et al.: Heart disease and stroke statistics-011 update: a report from the American Heart Association. / Circulation 2011,123(4):e18-e209. CrossRef
  2. Liu M, Wu B, Wang WZ, Lee LM, Zhang SH, Kong LZ: Stroke in China: epidemiology, prevention, and management strategies. / Lancet Neurol 2007,6(5):456-64. CrossRef
  3. Pillai DR, Dittmar MS, Baldaranov D, Heidemann RM, Henning EC, Schuierer G, Bogdahn U, Schlachetzki F: Cerebral ischemia-reperfusion injury in rats–a 3 T MRI study on biphasic blood–brain barrier opening and the dynamics of edema formation. / J Cereb Blood Flow Metab 2009,29(11):1846-855. CrossRef
  4. Tang XN, Cairns B, Kim JY, Yenari MA: NADPH oxidase in stroke and cerebrovascular disease. / Neurol Res 2012,34(4):338-45.
  5. Petrov VI, Ponomarev EA, Maskin SS, Strepetov NN: Pharmacological neuroprotection against brain damage in ischemiai/reperfusion experiment. / Eksp Klin Farmakol 2011,74(8):13-6.
  6. Muller-Eberhard U: Hemopexin. / N Engl J Med 1970,283(20):1090-094. CrossRef
  7. Camborieux L, Bertrand N, Swerts JP: Changes in expression and localization of hemopexin and its transcripts in injured nervous system: a comparison of central and peripheral tissues. / Neuroscience 1998,82(4):1039-052. CrossRef
  8. Kapojos JJ, van den Berg A, Van Goor H, Te LM, Poelstra K, Borghuis T, Bakker WW: Production of hemopexin by TNF-alpha stimulated human mesangial cells. / Kidney Int 2003,63(5):1681-686. CrossRef
  9. Tolosano E, Fagoonee S, Morello N, Vinchi F, Fiorito V: Heme scavenging and the other facets of hemopexin. / Antioxid Redox Signal 2010,12(2):305-20. CrossRef
  10. Li RC, Saleem S, Zhen G, Cao W, Zhuang H, Lee J, Smith A, Altruda F, Tolosano E, Dore S: Heme-hemopexin complex attenuates neuronal cell death and stroke damage. / J Cereb Blood Flow Metab 2009,29(5):953-64. CrossRef
  11. Yan W, Zhang H, Bai X, Lu Y, Dong H, Xiong L: Autophagy activation is involved in neuroprotection induced by hyperbaric oxygen preconditioning against focal cerebral ischemia in rats. / Brain Res 2011, 1402:109-21. CrossRef
  12. Garcia JH, Wagner S, Liu KF, Hu XJ: Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats. Statistical validation. / Stroke Stroke 1995,26(4):627-35. CrossRef
  13. Xiong L, Zheng Y, Wu M, Hou L, Zhu Z, Zhang X, Lu Z: Preconditioning with isoflurane produces dose-dependent neuroprotection via activation of adenosine triphosphate-regulated potassium channels after focal cerebral ischemia in rats. / Anesth Analg 2003,96(1):233-37.
  14. Wang Q, Peng Y, Chen S, Gou X, Hu B, Du J, Lu Y, Xiong L: Pretreatment with electroacupuncture induces rapid tolerance to focal cerebral ischemia through regulation of endocannabinoid system. / Stroke 2009,40(6):2157-164. CrossRef
  15. Takahashi N, Takahashi Y, Putnam FW: Complete amino acid sequence of human hemopexin, the heme-binding protein of serum. / Proc Natl Acad Sci USA 1985,82(1):73-7. CrossRef
  16. Gutteridge JM: Lipid peroxidation and antioxidants as biomarkers of tissue damage. / Clin Chem 1995,41(12 Pt 2):1819-828.
  17. Barnard ML, Muller-Eberhard U, Turrens JF: Protective role of hemopexin on heme-dependent lung oxidative stress. / Biochem Biophys Res Commun 1993,192(1):82-7. CrossRef
  18. Brass CA, Immenschuh S, Song DX, Liem HH, Eberhard UM: Hemopexin decreases spontaneous chemiluminescence of cold preserved liver after reperfusion. / Biochem Biophys Res Commun 1998,248(3):574-77. CrossRef
  19. Chen CC, Lu YC, Chen YW, Lee WL, Lu CH, Chen YH, Lee YC, Lin ST, Timms JF, Lee YR, / et al.: Hemopexin is up-regulated in plasma from type 1 diabetes mellitus patients: role of glucose-induced ROS. / J Proteomics 2012,75(12):3760-777. CrossRef
  20. Dang TN, Bishop GM, Dringen R, Robinson SR: The metabolism and toxicity of hemin in astrocytes. / Glia 2011,59(10):1540-550. CrossRef
  21. Dang TN, Robinson SR, Dringen R: / Bishop. Uptake, metabolism and toxicity of hemin in cultured neurons. Neurochem Int: GM; 2011.
  22. Vincent SH, Grady RW, Shaklai N, Snider JM, Muller-Eberhard U: The influence of heme-binding proteins in heme-catalyzed oxidations. / Arch Biochem Biophys 1988,265(2):539-50. CrossRef
  23. Davies DM, Smith A, Muller-Eberhard U, Morgan WT: Hepatic subcellular metabolism of heme from heme-hemopexin: incorporation of iron into ferritin. / Biochem Biophys Res Commun 1979,91(4):1504-511. CrossRef
  24. Chen-Roetling J, Liu W, Regan RF: Hemopexin decreases hemin accumulation and catabolism by neural cells. / Neurochem Int 2012,60(5):488-94. CrossRef
  25. Immenschuh S, Nagae Y, Satoh H, Baumann H, Muller-Eberhard U: The rat and human hemopexin genes contain an identical interleukin-6 response element that is not a target of CAAT enhancer-binding protein isoforms. / J Biol Chem 1994,269(17):12654-2661.
  26. Immenschuh S, Song DX, Satoh H, Muller-Eberhard U: The type II hemopexin interleukin-6 response element predominates the transcriptional regulation of the hemopexin acute phase responsiveness. / Biochem Biophys Res Commun 1995,207(1):202-08. CrossRef
  27. Huang J, Upadhyay UM, Tamargo RJ: Inflammation in stroke and focal cerebral ischemia. / Surg Neurol 2006,66(3):232-45. CrossRef
  28. Tsuchihashi S, Fondevila C, Kupiec-Weglinski JW: Heme oxygenase system in ischemia and reperfusion injury. / Ann Transplant 2004,9(1):84-7.
  29. Eskew JD, Vanacore RM, Sung L, Morales PJ, Smith A: Cellular protection mechanisms against extracellular heme. heme-hemopexin, but not free heme, activates the N-terminal c-jun kinase. / J Biol Chem 1999,274(2):638-48. CrossRef
  30. Schuller E, Delasnerie N, Moreno P, Tompe L: Electro-immunodiffusion of the proteins of the cerebrospinal fluid: determination of 1 -lipoprotein, 1 -E(C'4) and 2 -glycoprotein I. / Clin Chim Acta 1972,39(1):233-38. CrossRef
  31. Schuller E, Allinquant B, Garcia M, Lefevre M, Moreno P, Tompe L: Electro-immunodiffusion of cerebrospinal fluid proteins. Determination of 2 -HS, ceruloplasmin, - 1A - 1C , hemopexin and IgA. / Clin Chim Acta 1971,33(1):5-1. CrossRef
  
• 作者单位：Beibei Dong (1)
  Min Cai (1)
  Zongping Fang (1)
  Haidong Wei (1)
  Fangyun Zhu (1)
  Guochao Li (1)
  Hailong Dong (1)
  Lize Xiong (2)
  
  1. Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shanxi, 710032, China
  2. Key Laboratory of the Critical Care Medicine of PLA, Xijing Hospital, the Fourth Military Medical University, Xi’an, Shanxi, 710032, China
  

文摘

Background The plasma protein hemopexin (HPX) exhibits the highest binding affinity to free heme. In vitro experiments and gene-knock out technique have suggested that HPX may have a neuroprotective effect. However, the expression of HPX in the brain was not well elucidated and its expression after cerebral ischemia-reperfusion injury was also poorly studied. Furthermore, no in vivo data were available on the effect of HPX given centrally on the prognosis of focal cerebral ischemia. Results In the present study, we systematically investigated expression of HPX in normal rat brain by immunofluorescent staining. The results showed that HPX was mainly expressed in vascular system and neurons, as well as in a small portion of astrocytes adjacent to the vessels in normal rat brain. Further, we determined the role of HPX in the process of focal cerebral ischemic injury and explored the effects of HPX treatment in a rat model of transient focal cerebral ischemia. After 2 h-middle cerebral artery occlusion (MCAO) followed by 24 h-reperfusion, the expression of HPX was increased in the neurons and astrocytes in the penumbra area, as demonstrated by immunohistochemistry and Western blot techniques. Intracerebroventricular injection of HPX at the onset of reperfusion dose-dependently reduced the infarct volumes and improved measurements of neurological function of the rat subjected to transient focal cerebral ischemia. The neuroprotective effects of HPX sustained for up to 7 days after experiments. Conclusions Our study provides a new insight into the potential neuroprotective role of HPX as a contributing factor of endogenous protective mechanisms against focal cerebral ischemia injury, and HPX might be developed as a potential agent for treatment of ischemic stroke.