Abstract
Caspase-12 has been localized to endoplasmic reticulum (ER) and showed to involve ER stress-induced apoptosis. In the present work we investigated the temporospatial alterations of caspase-12 immunoreactivity in the penumbra following cerebral ischemia/reperfusion in rabbit. Transient cerebral ischemia was produced by intraluminal occlusion of the middle cerebral artery for 2 h followed by 1 h, 6 h, 1 day, 3 days, 7 days and 14 days of reperfusion. Caspase-12 immunohistochemistry was first increased in the penumbra 1 h after reperfusion, with a peak at day 1 to day 3, and then gradually decreased to basal level at day 14. The number of TUNEL-positive cells and ultrastructural observation of brain sections in the penumbra showed a similar change at the same time points. ER mediated by caspase-12 participated in apoptosis induced by cerebral ischemia/reperfusion injury, which may provide a new area for therapeutic intervention to ameliorate outcomes following cerebral ischemia.
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References
Rao RV, Ellerby HM, Bredesen DE (2004) Coupling endoplasmic reticulum stress to the cell death program. Cell Death Differ 11:372–380
Kumar R, Krause GS, Yoshida H et al (2003) Dysfunction of the unfolded protein response during global brain ischemia and reperfusion. J Cereb Blood Flow Metab 23:462–471
Paschen W, Doutheil J (1999) Disturbances of the functioning of endoplasmic reticulum: a key mechanism underlying neuronal cell injury? J Cereb Blood Flow Metab 19:1–18
Tajiri S, Oyadomari S, Yano S et al (2004) Ischemia-induced neuronal cell death is mediated by the endoplasmic reticulum stress pathway involving CHOP. Cell Death Differ 11:403–415
Nakagawa T, Zhu H, Morishima N et al (2000) Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature 403:98–103
Mouw G, Zechel JL, Gamboa J et al (2003) Activation of caspase-12, an endoplasmic reticulum resident caspase, after permanent focal ischemiain rat. Neuro Report 14:183–186
Mouw G, Zechel JL, Zhou Y et al (2002) Caspase-9 inhibition after focal cerebral ischemia improves outcome following reversible focal ischemia. Metab Brain Dis 17:143–151
Shibata M, Hattori H, Sasaki T (2003) Activation of caspase-12 by endoplasmic reticulum stress induced by transient middle cerebral artery occlusion in mice. Neuroscience 118:491–499
Yang JP, Liu XF, Liu HJ et al (2008) Extracellular signal-regulated kinase involved in NGF/VEGF-induced neuroprotective effect. Neurosci Lett 434:212–217
Nabavi DG, Cenic A, Henderson S et al (2001) Perfusion mapping using computed tomography allows accurate prediction of cerebral infarction in experimental brain ischemia. Stroke 32:175–183
Manabat C, Han BH, Wendland M et al (2003) Reperfusion differentially induces caspase-3 activation in ischemic core and penumbra after stroke in immature brain. Stroke 34:207–213
Linnik MD, Miller JA, Sprinkle-Cavallo J et al (1995) Apoptosis DNA fragmentation in the rat cerebral cortex induced by permanent middle cerebral artery occlusion. Mol Brain Res 32:116–124
Korde AS, Pettigrew LC, Craddock SD et al (2005) The mitochondrial uncoupler 2, 4-dinitrophenol attenuates tissue damage and improves mitochondrial homeostasis following transient focal cerebral ischemia. J Neurochem 94:1676–1684
Lo EH, Dalkara T, Moskowitz MA (2003) Mechanisms, challenges and opportunities in stroke. Nat Rev Neurosci 4:399–415
Unal-Cevik I, Kilinc M, Can A et al (2004) Apoptotic and necrotic death mechanisms are concomitantly activated in the same cell after cerebral ischemia. Stroke 35:2189–2194
Rao V, Poksay KS, Castro-Obregon S et al (2004) Molecular components of a cell death pathway activated by endoplasmic reticulum stress. J Biol Chem 279:177–187
Yoneda T, Imaizumi K, Oono K et al (2001) Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependent mechanism in response to the ER stress. J Biol Chem 276:13935–13940
Acknowledgments
This study was supported by China Ministry of Health Science Foundation (#200310, Dr. Liu), Hebei Natural Science Foundation (#C2006000927, Dr. Liu). China Postdoctor Science Foundation (#20070411051, Dr. Yang).
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Liu, Hj., Yang, JP., Wang, CH. et al. Endoplasmic reticulum in the penumbra following middle cerebral artery occlusion in the rabbit. Neurol Sci 30, 227–232 (2009). https://doi.org/10.1007/s10072-009-0086-y
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DOI: https://doi.org/10.1007/s10072-009-0086-y