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Aging and Disease    2014, Vol. 5 Issue (6) : 366-372     DOI: 10.14336/AD.2014.0500366
Original Article |
Reduced Apoptosis by Ethanol and Its Association with PKC-δ and Akt Signaling in Ischemic Stroke
Hafeez Adam1, Elmadhoun Omar1, Peng Changya1, Y. Ding Jamie2, Geng Xiaokun1, Guthikonda Murali1, Ding Yuchuan1, *()
1Department of Neurological Surgery, Wayne State University School of Medicine, Detroit, Michigan, USA
2Princeton University, Princeton, New Jersey, USA
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Abstract  

Along with thrombolytic therapy, which has a number of limitations, stroke outcome may be improved with neuroprotective therapies that disrupt ischemic cell death. Recent research has shown a neuroprotective role of ethanol administration during ischemic stroke, such as its ability to reduce infarct volume and neurologic deficit. In order to investigate this further, we assessed the hypothesis that ethanol’s neuroprotective effect is through reduction of apoptosis and the modulation of the important apoptotic PKC-δ and Akt signaling pathway. Ethanol (1.5 g/kg) was given by intraperitoneal injections to 54 Sprague-Dawley rats after 2 hours of middle cerebral artery (MCA) occlusion, followed by 3 or 24 hours of reperfusion. We measured apoptotic cell death, PKC-δ, and Akt mRNA and protein expressions in each of ischemic groups with or without ethanol treatment using ELISA, real-time PCR and Western blot analysis. Our results showed that cell death was significantly increased in rats following 2 hour MCA occlusion and 24 hour reperfusion. Subsequently, cell death was significantly reduced by an administration of ethanol. We further found that ethanol administration, prior to either 3 or 24 hours of reperfusion, significantly decreased the expression of PKC-δ while simultaneously increasing the expression Akt at both mRNA and protein levels at the two points. In conclusion, our study suggests that ethanol administration following ischemic stroke modulates the gene and protein profile in such a way that it increased expression of anti-apoptotic Akt and decreased the pro-apoptotic PKC-δ. This ultimately results in a decrease in neuronal apoptosis, thus conferring neuroprotection.

Keywords Ischemia/reperfusion      neuroprotection      apoptosis      ethanol      PKC-δ      Akt/PKB     
Corresponding Authors: Ding Yuchuan     E-mail: yding@med.wayne.edu
Issue Date: 21 November 2014
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Hafeez Adam
Elmadhoun Omar
Peng Changya
Y. Ding Jamie
Geng Xiaokun
Guthikonda Murali
Ding Yuchuan
Cite this article:   
Hafeez Adam,Elmadhoun Omar,Peng Changya, et al. Reduced Apoptosis by Ethanol and Its Association with PKC-δ and Akt Signaling in Ischemic Stroke[J]. Aging and Disease, 2014, 5(6): 366-372.
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http://www.aginganddisease.org/EN/10.14336/AD.2014.0500366     OR     http://www.aginganddisease.org/EN/Y2014/V5/I6/366
[1] Hacke W, Donnan G, Fieschi C, Kaste M, von Kummer R, Broderick JP, et al. (2004). Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet, 363: 768-774
[2] Broughton BR, Reutens DC, Sobey CG (2009). Apoptotic mechanisms after cerebral ischemia. Stroke;a journal of cerebral circulation, 40: e331-339
[3] Wang F, Wang Y, Geng X, Asmaro K, Peng C, Sullivan JM, et al. (2012). Neuroprotective effect of acute ethanol administration in a rat with transient cerebral ischemia. Stroke;. a journal of cerebral circulation, 43: 205-210
[4] Fu P, Peng C, Ding JY, Asmaro K, Sullivan JM, Guthikonda M, et al. (2013). Acute administration of ethanol reduces apoptosis following ischemic stroke in rats. Neuroscience research, 76: 93-97
[5] Yuan Y, Peng C, Li K, Hussain M, Sikharam C, Guthikonda M, et al. (2012). Ethanol reduces expression of apoptotic proteins after hypoxia/reoxygenation in a brain slice model. Neurological research, 34: 373-378
[6] Elmore S (2007). Apoptosis: a review of programmed cell death. Toxicologic pathology, 35: 495-516
[7] Saelens X, Festjens N, Vande Walle L, van Gurp M, van Loo G, Vandenabeele P (2004). Toxic proteins released from mitochondria in cell death. Oncogene, 23: 2861-2874
[8] Dave KR, Bhattacharya SK, Saul I, DeFazio RA, Dezfulian C, Lin HW, et al. (2011). Activation of protein kinase C delta following cerebral ischemia leads to release of cytochrome C from the mitochondria via bad pathway. PloS one, 6: e22057
[9] Zhao H, Sapolsky RM, Steinberg GK (2006). Phosphoinositide-3-kinase/akt survival signal pathways are implicated in neuronal survival after stroke. Molecular neurobiology, 34: 249-270
[10] Longa EZ, Weinstein PR, Carlson S, Cummins R (1989). Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke; a journal of cerebral circulation, 20: 84-91
[11] Geng X, Parmar S, Li X, Peng C, Ji X, Chakraborty T, et al. (2013). Reduced apoptosis by combining normobaric oxygenation with ethanol in transient ischemic stroke. Brain Res, 1531: 17-24
[12] Hayes K, Sprague S, Guo M, Davis W, Friedman A, Kumar A, et al. (2008). Forced, not voluntary, exercise effectively induces neuroprotection in stroke. Acta neuropathologica, 115: 289-296
[13] Geng X, Parmar S, Li X, Peng C, Ji X, Chakraborty T, et al. (2013). Reduced apoptosis by combining normobaric oxygenation with ethanol in transient ischemic stroke. Brain Research, 1531: 17-24
[14] Chou WH, Messing RO (2005). Protein kinase C isozymes in stroke. Trends in cardiovascular medicine, 15: 47-51
[15] Gliki G, Wheeler-Jones C, Zachary I (2002). Vascular endothelial growth factor induces protein kinase C (PKC)-dependent Akt/PKB activation and phosphatidylinositol 3'-kinase-mediates PKC delta phosphorylation: role of PKC in angiogenesis. Cell biology international, 26: 751-759
[16] Taylor JM, Crack PJ (2004). Impact of oxidative stress on neuronal survival. Clinical and experimental pharmacology & physiology, 31: 397-406
[17] Zhao H (2009). Ischemic postconditioning as a novel avenue to protect against brain injury after stroke. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 29: 873-885
[18] Zhong M, Lu Z, Foster DA (2002). Downregulating PKC delta provides a PI3K/Akt-independent survival signal that overcomes apoptotic signals generated by c-Src overexpression. Oncogene, 21: 1071-1078
[19] Gao X, Zhang H, Takahashi T, Hsieh J, Liao J, Steinberg GK, et al. (2008). The Akt signaling pathway contributes to postconditioning's protection against stroke; the protection is associated with the MAPK and PKC pathways. Journal of neurochemistry, 105: 943-955
[20] Lawlor MA, Alessi DR (2001). PKB/Akt: a key mediator of cell proliferation, survival and insulin responses? Journal of cell science, 114: 2903-2910
[21] Cho H, Mu J, Kim JK, Thorvaldsen JL, Chu Q, Crenshaw EB, et al. (2001). Insulin Resistance and a Diabetes Mellitus-Like Syndrome in Mice Lacking the Protein Kinase Akt2 (PKBβ). Science, 292: 1728-1731
[22] Wen HC, Huang WC, Ali A, Woodgett JR, Lin WW (2003). Negative regulation of phosphatidylinositol 3-kinase and Akt signalling pathway by PKC. Cellular signalling, 15: 37-45
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