PI3K/Akt pathway contributes to neurovascular unit protection of Xiao-Xu-Ming decoction against focal cerebral ischemia and reperfusion injury in rats

Evidence-based Complementary and Alternative Medicine

Volumn 2013, Issue , 2013, Pages

  Lan, Rui ^a   Xiang, Jun ^a,b   Zhang, Yong ^c   Wang, Guo Hua ^a   Bao, Jie ^b   Li, Wen Wei ^a   Zhang, Wen ^a   Xu, Li Li ^a   Cai, Ding Fang ^a  

^a FUDAN UNIVERSITY   (China)

^b SHANGHAI UNIVERSITY OF TRADITIONAL CHINESE MEDICINE   (China)

^c GUANGZHOU UNIVERSITY OF CHINESE MEDICINE   (China)

Author keywords

[No Author keywords available]

Indexed keywords

2 MORPHOLINO 8 PHENYLCHROMONE; HERBACEOUS AGENT; NEUROPROTECTIVE AGENT; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; UNCLASSIFIED DRUG; XIAO XU MING DECOCTION;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN FUNCTION; BRAIN INFARCTION; BRAIN ISCHEMIA; CONTROLLED STUDY; DNA FRAGMENTATION; IMMUNOFLUORESCENCE; MALE; MIDDLE CEREBRAL ARTERY OCCLUSION; NERVE CELL LESION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; REPERFUSION INJURY; UPREGULATION; WESTERN BLOTTING;

EID: 84879289244     PISSN: 1741427X     EISSN: 17414288     Source Type: Journal    
DOI: 10.1155/2013/459467     Document Type: Article

References (75)

1. Lo E. H., Dalkara T., Moskowitz M. A., Mechanisms, challenges and opportunities in stroke. Nature Reviews Neuroscience 2003 4 5 399 415 2-s2.0-0037868093 10.1038/nrn1106
2. Vangilder R. L., Rosen C. L., Barr T. L., Huber J. D., Targeting the neurovascular unit for treatment of neurological disorders. Pharmacology and Therapeutics 2011 130 3 239 247 2-s2.0-79955599523 10.1016/j.pharmthera.2010.12. 004
3. Liu R., Zhang T. T., Wu C. X., Lan X., Du G. H., Targeting the neurovascular unit: development of a new model and consideration for novel strategy for Alzheimer's disease. Brain Research Bulletin 2011 86 1-2 13 21
4. Broughton B. R. S., Reutens D. C., Sobey C. G., Apoptotic mechanisms after cerebral ischemia. Stroke 2009 40 5 e331 e339 2-s2.0-65549098614 10.1161/STROKEAHA.108.531632
5. Hou S. T., MacManus J. P., Molecular mechanisms of cerebral ischemia-induced neuronal death. International Review of Cytology 2002 221 93 148 2-s2.0-0036445163 10.1016/S0074-7696(02)21011-6
6. Zhu Y. M., Wang C. C., Chen L., Qian L. B., Ma L. L., Yu J., Zhu M. H., Wen C. Y., Yu L. N., Yan M., Both PI3K/Akt and ERK1/2 pathways participate in the protection by dexmedetomidine against transient focal cerebral ischemia/reperfusion injury in rats. Brain Research 2013 1494 1 8
7. Endo H., Nito C., Kamada H., Nishi T., Chan P. H., Activation of the Akt/GSK3 β signaling pathway mediates survival of vulnerable hippocampal neurons after transient global cerebral ischemia in rats. Journal of Cerebral Blood Flow and Metabolism 2006 26 12 1479 1489 2-s2.0-33751331389 10.1038/sj.jcbfm.9600303
8. Zhao H., Sapolsky R. M., Steinberg G. K., Phosphoinositide-3-kinase/Akt survival signal pathways are implicated in neuronal survival after stroke. Molecular Neurobiology 2006 34 3 249 269 2-s2.0-33847014888 10.1385/MN:34:3:249
9. Saito A., Hayashi T., Okuno S., Ferrand-Drake M., Chan P. H., Overexpression of copper/zinc superoxide dismutase in transgenic mice protects against neuronal cell death after transient focal ischemia by blocking activation of the bad cell death signaling pathway. Journal of Neuroscience 2003 23 5 1710 1718 2-s2.0-0037335444
10. Kawano T., Morioka M., Yano S., Hamada J. I., Ushio Y., Miyamoto E., Fukunaga K., Decreased Akt activity is associated with activation of forkhead transcription factor after transient forebrain ischemia in gerbil hippocampus. Journal of Cerebral Blood Flow and Metabolism 2002 22 8 926 934 2-s2.0-0036325163
11. Zhang J., Deng Z., Liao J., Song C., Liang C., Xue H., Wang L., Zhang K., Yan G., Leptin attenuates cerebral ischemia injury through the promotion of energy metabolism via the PI(3)K/Akt pathway. Journal of Cerebral Blood Flow & Metabolism 2013 33 4 567 574 10.1038/jcbfm.2012.202
12. Mackensen G. B., Patel M., Sheng H., Calvi C. L., Batinić-Haberle I., Day B. J., Liang L. P., Fridovich I., Crapo J. D., Pearlstein R. D., Warner D. S., Neuroprotection from delayed postischemic administration of a metalloporphyrin catalytic antioxidant. Journal of Neuroscience 2001 21 13 4582 4592 2-s2.0-0035399884
13. Xing B., Chen H., Zhang M., Zhao D., Jiang R., Liu X., Zhang S., Ischemic postconditioning inhibits apoptosis after focal cerebral ischemia/reperfusion injury in the rat. Stroke 2008 39 8 2362 2369 2-s2.0-49849103054 10.1161/STROKEAHA.107.507939
14. Li S. Y., Yang D., Fu Z. J., Woo T., Wong D., Lo A. C., Lutein enhances survival and reduces neuronal damage in a mouse model of ischemic stroke. Neurobiology of Disease 2012 45 1 624 632
15. Baliga S. S., Jaques-Robinson K. M., Hadzimichalis N. M., Golfetti R., Merrill G. F., Acetaminophen reduces mitochondrial dysfunction during early cerebral postischemic reperfusion in rats. Brain Research 2010 1319 142 154 2-s2.0-76849094630 10.1016/j.brainres.2010.01.013
16. Gelderblom M., Leypoldt F., Lewerenz J., Birkenmayer G., Orozco D., Ludewig P., Thundyil J., Arumugam T. V., Gerloff C., Tolosa E., Maher P., Magnus T., The flavonoid fisetin attenuates postischemic immune cell infiltration, activation and infarct size after transient cerebral middle artery occlusion in mice. Journal Cerebral Blood Flow & Metabolism 2012 32 5 835 843
17. Zhang R. L., Chopp M., Jiang N., Wen Xue Tang, Prostak J., Manning A. M., Anderson D. C., Feuerstein G. Z., Barone F. C., Anti-intercellular adhesion molecule-1 antibody reduces ischemic cell damage after transient but not permanent middle cerebral artery occlusion in the Wistar rat. Stroke 1995 26 8 1438 1443 2-s2.0-0029096735
18. Kawasaki-Yatsugi S., Ichiki C., Yatsugi S. I., Takahashi M., Shimizu-Sasamata M., Yamaguchi T., Minematsu K., Neuroprotective effects of an AMPA receptor antagonist YM872 in a rat transient middle cerebral artery occlusion model. Neuropharmacology 2000 39 2 211 217 2-s2.0-0033988426 10.1016/S0028-3908(99)00117-3
19. Baba T., Kameda M., Yasuhara T., Kondo T. M. A., Shingo T., Tajiri N., Wang F., Miyoshi Y., Borlongan C. V., Matsumae M., Date I., Electrical stimulation of the cerebral cortex exerts antiapoptotic, angiogenic, and anti-inflammatory effects in ischemic stroke rats through phosphoinositide 3-kinase/akt signaling pathway. Stroke 2009 40 11 e598 e605 2-s2.0-70350558543 10.1161/STROKEAHA.109.563627
20. Berthet C., Lei H., Thevenet J., Gruetter R., Magistretti P. J., Hirt L., Neuroprotective role of lactate after cerebral ischemia. Journal of Cerebral Blood Flow and Metabolism 2009 29 11 1780 1789 2-s2.0-71949099751 10.1038/jcbfm.2009.97
21. Ros J., Pecinska N., Alessandri B., Landolt H., Fillenz M., Lactate reduces glutamate-induced neurotoxicity in rat cortex. Journal of Neuroscience Research 2001 66 5 790 794 2-s2.0-0035577774 10.1002/jnr.10043
22. Cheng Y. D., Al-Khoury L., Zivin J. A., Neuroprotection for ischemic stroke: two decades of success and failure. The Journal of The American Society for Experimental NeuroTherapeutics 2004 1 1 36 45 2-s2.0-19544376511 10.1602/neurorx.1.1.36
23. Huang P., Zhou C. M., Qin-Hu, Liu Y. Y., Hu B. H., Chang X., Zhao X. R., Xu X. S., Li Q., Wei X. H., Mao X. W., Wang C. S., Fan J. Y., Han J. Y., Cerebralcare Granule(R) attenuates blood-brain barrier disruption after middle cerebral artery occlusion in rats. Experimental Neurology 2012 237 2 453 463
24. Xiang J., Tang Y. P., Wu P., Gao J. P., Cai D. F., Chinese medicine Nao-Shuan-Tong attenuates cerebral ischemic injury by inhibiting apoptosis in a rat model of stroke. Journal of Ethnopharmacology 2010 131 1 174 181 2-s2.0-77955329651 10.1016/j.jep.2010.06.021
25. Wang H. W., Liou K. T., Wang Y. H., Lu C. K., Lin Y. L., Lee I. J., Huang S. T., Tsai Y. H., Cheng Y. C., Lin H. J., Shen Y. C., Deciphering the neuroprotective mechanisms of Bu-yang Huan-wu decoction by an integrative neurofunctional and genomic approach in ischemic stroke mice. Journal of Ethnopharmacology 2011 138 1 22 33
26. Li X. M., Bai X. C., Qin L. N., Huang H., Xiao Z. J., Gao T. M., Neuroprotective effects of Buyang Huanwu Decoction on neuronal injury in hippocampus after transient forebrain ischemia in rats. Neuroscience Letters 2003 346 1-2 29 32 2-s2.0-0038383786 10.1016/S0304-3940(03)00522-6
27. Lee J. J., Hsu W. H., Yen T. L., Chang N. C., Luo Y. J., Hsiao G., Sheu J. R., Traditional Chinese medicine, Xue-Fu-Zhu-Yu decoction, potentiates tissue plasminogen activator against thromboembolic stroke in rats. Journal of Ethnopharmacology 2011 134 3 824 830 2-s2.0-79954419856 10.1016/j.jep.2011.01. 033
28. Zhu X. H., Li S. J., Hu H. H., Sun L. R., Das M., Gao T. M., Neuroprotective effects of Xiao-Xu-Ming decoction against ischemic neuronal injury in vivo and in vitro. Journal of Ethnopharmacology 2010 127 1 38 46 2-s2.0-72149117930 10.1016/j.jep.2009.09.054
29. Wang Y. H., He X. L., Yang H. G., Qin H. L., Du G. H., Effects of the effective components groups of Xiao-Xu-Ming decoction on MCAO rats Chinese Pharmaceutical Journal 2012 47 3 94 198
30. Wang Y. H., He X. L., Lee X. X., Qin H. L., Du G. H., Effects of the effective component group of Chinese herbal medicine Xiao-Xu-Ming decoction on brain mitochondria in rats with chronic cerebral ischemia Journal of Chinese Integrative Medicine 2012 10 5 569 576
31. Cai D. F., Yang Y. K., Gu X. X., Clinical trial on treatment of acute cerebral infarction with TCM treatment according to syndrome differentiation combining Western medicine by staging Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine / Zhongguo Zhong xi yi jie he xue hui, Zhongguo Zhong yi yan jiu yuan zhu ban 2007 27 9 789 792 2-s2.0-58149180287
32. Zhou S., Clinical Research on Xiao-Xu-Ming decoction treating the stroke patients with neurological deficits Journal of New Chinese Medicine 2011 43 5 17 18
33. Huang J. H., Huang X. H., Chen Z. Y., Zheng Q. S., Sun R. Y., Dose conversion among different animals and healthy volunteers in pharmacological study Chinese Journal of Clinical Pharmacology and Therapeutics 2004 9 9 1069 1072
34. Xiang J., Lan R., Tang Y. P., Chen Y. P., Cai D. F., Apocynum venetum leaf extract attenuates disruption of the blood-brain barrier and upregulation of matrix metalloproteinase-9/-2 in a rat model of cerebral ischemia-reperfusion injury. Neurochemical Research 2012 37 8 1820 1828
35. Zarow G. J., Karibe H., States B. A., Graham S. H., Weinstein P. R., Endovascular suture occlusion of the middle cerebral artery in rats: effect of suture insertion distance on cerebral blood flow, infarct distribution and infarct volume. Neurological Research 1997 19 4 409 416 2-s2.0-0030737572
36. Schmid-Elsaesser R., Zausinger S., Hungerhuber E., Baethmann A., Reulen H. J., A critical reevaluation of the intraluminal thread model of focal cerebral ischemia: evidence of inadvertent premature reperfusion and subarachnoid hemorrhage in rats by laser-Doppler flowmetry. Stroke 1998 29 10 2162 2170 2-s2.0-0031665617
37. Zhao Q., Memezawa H., Smith M. L., Siesjo B. K., Hyperthermia complicates middle cerebral artery occlusion induced by an intraluminal filament. Brain Research 1994 649 1-2 253 259 2-s2.0-0028365406 10.1016/0006-8993(94)91071-5
38. Sicard K. M., Fisher M., Animal models of focal brain ischemia. Experimental & Translational Stroke Medicine 2009 1 article 7
39. Zhao H., Shimohata T., Wang J. Q., Sun G., Schaal D. W., Sapolsky R. M., Steinberg G. K., Akt contributes to neuroprotection by hypothermia against cerebral ischemia in rats. Journal of Neuroscience 2005 25 42 9794 9806 2-s2.0-27144446140 10.1523/JNEUROSCI.3163-05.2005
40. Paxinos G., Watson C., The Rat Brain in Stereotaxic Coordinates, Compact 1997 3rd California, Calif, USA San Diego Academic Press
41. Hara H., Huang P. L., Panahian N., Fishman M. C., Moskowitz M. A., Reduced brain edema and infarction volume in mice lacking the neuronal isoform of nitric oxide synthase after transient MCA occlusion. Journal of Cerebral Blood Flow and Metabolism 1996 16 4 605 611 2-s2.0-0029976959
42. Zhou C., Tu J., Zhang Q., Lu D., Zhu Y., Zhang W., Yang F., Brann D. W., Wang R., Delayed ischemic postconditioning protects hippocampal CA1 neurons by preserving mitochondrial integrity via Akt/GSK3beta signaling. Neurochemistry International 2011 59 6 749 758
43. Del Zoppo G. J., Poeck K., Pessin M. S., Wolpert S. M., Furlan A. J., Ferbert A., Alberts M. J., Zivin J. A., Wechsler L., Busse O., Greenlee R., Brass L., Mohr J. P., Feldmann E., Hacke W., Kase C. S., Biller J., Gress D., Otis S. M., Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke. Annals of Neurology 1992 32 1 78 86 2-s2.0-0026759412 10.1002/ana.410320113
44. Li Z., Ni K., Du G., Simultaneous analysis of six effective components in the anti-Alzheimer's disease effective component group of Xiao-Xu-Ming decoction Chinese Journal of Chromatography (Se Pu) 2007 25 1 80 83 2-s2.0-57149122998
45. Du K., Wu C., Ding C., Zhao S., Qin H., Zhang J., Simultaneous LC-MS analysis and of wogonin and oroxylin a in rat plasma, and pharmacokinetic studies after administration of the active fraction from Xiao-Xu-Ming decoction. Chromatographia 2009 69 11-12 1259 1266 2-s2.0-67649992563 10.1365/s10337-009- 1072-5
46. Wang Y., Ding C., Du K., Xiao Y., Wu C., Zhang J., Qin H., Du G., Identification of active compounds and their metabolites by high-performance liquid chromatography/electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry from Xiao-Xu-Ming decoction (XXMD). Rapid Communications in Mass Spectrometry 2009 23 17 2724 2732 2-s2.0-69249126533 10.1002/rcm.4179
47. Tang N. Y., Liu C. H., Hsieh C. T., Hsieh C. L., The anti-inflammatory effect of paeoniflorin on cerebral infarction induced by ischemia-reperfusion injury in sprague-dawley rats. American Journal of Chinese Medicine 2010 38 1 51 64 2-s2.0-77951239196 10.1142/S0192415X10007786
48. Chen D. M., Xiao L., Cai X., Zeng R., Zhu X. Z., Involvement of multitargets in paeoniflorin-induced preconditioning. Journal of Pharmacology and Experimental Therapeutics 2006 319 1 165 180 2-s2.0-33749024778 10.1124/jpet.106.104380
49. Xiao L., Wang Y. Z., Liu J., Luo X. T., Ye Y., Zhu X. Z., Effects of paeoniflorin on the cerebral infarction, behavioral and cognitive impairments at the chronic stage of transient middle cerebral artery occlusion in rats. Life Sciences 2005 78 4 413 420 2-s2.0-27744529453 10.1016/j.lfs.2005.04.069
50. Tu X. K., Yang W. Z., Liang R. S., Shi S. S., Chen J. P., Chen C. M., Wang C. H., Xie H. S., Chen Y., Ouyang L. Q., Effect of baicalin on matrix metalloproteinase-9 expression and blood-brain barrier permeability following focal cerebral ischemia in rats. Neurochemical Research 2011 36 11 2022 2028
51. Xue X., Qu X. J., Yang Y., Sheng X. H., Cheng F., Jiang E. N., Wang J. H., Bu W., Liu Z. P., Baicalin attenuates focal cerebral ischemic reperfusion injury through inhibition of nuclear factor B p65 activation. Biochemical and Biophysical Research Communications 2010 403 3-4 398 404 2-s2.0-78650170987 10.1016/j.bbrc.2010.11.042
52. Tu X. K., Yang W. Z., Shi S. S., Chen Y., Wang C. H., Chen C. M., Chen Z., Baicalin inhibits TLR2/4 signaling pathway in rat brain following permanent cerebral ischemia. Inflammation 2011 34 5 463 470
53. Tu X. K., Yang W. Z., Shi S. S., Wang C. H., Chen C. M., Neuroprotective effect of baicalin in a rat model of permanent focal cerebral ischemia. Neurochemical Research 2009 34 9 1626 1634 2-s2.0-68349131159 10.1007/s11064-009-9953-4
54. Cho J., Lee H. K., Wogonin inhibits ischemic brain injury in a rat model of permanent middle cerebral artery occlusion. Biological and Pharmaceutical Bulletin 2004 27 10 1561 1564 2-s2.0-21644489720 10.1248/bpb.27.1561
55. Hua Z. P., Shun A. J., Hyang S. C., Lee J. C., Kim W. K., Neuroprotective effect of wogonin: potential roles of inflammatory cytokines. Archives of Pharmacal Research 2004 27 9 930 936 2-s2.0-16644397756
56. van Leyen K., Kim H. Y., Lee S. R., Jin G., Arai K., Lo E. H., Baicalein and 12/15-lipoxygenase in the ischemic brain. Stroke 2006 37 12 3014 3018 2-s2.0-33845442015 10.1161/01.STR.0000249004.25444.a5
57. Xu Y. W., Sun L., Liang H., Sun G. M., Cheng Y., 12/15-Lipoxygenase inhibitor baicalein suppresses PPAR γ expression and nuclear translocation induced by cerebral ischemia/reperfusion. Brain Research 2010 1307 149 157 2-s2.0-70749160209 10.1016/j.brainres.2009.10.038
58. Cui L., Zhang X., Yang R., Liu L., Wang L., Li M., Du W., Baicalein is neuroprotective in rat MCAO model: role of 12/15-lipoxygenase, mitogen-activated protein kinase and cytosolic phospholipase A2. Pharmacology Biochemistry and Behavior 2010 96 4 469 475 2-s2.0-77956059859 10.1016/j.pbb.2010.07.007
59. Liu C., Wu J., Xu K., Cai F., Gu J., Ma L., Chen J., Neuroprotection by baicalein in ischemic brain injury involves PTEN/AKT pathway. Journal of Neurochemistry 2010 112 6 1500 1512 2-s2.0-77349112413 10.1111/j.1471-4159.2009. 06561.x
60. Lapchak P. A., Maher P., Schubert D., Zivin J. A., Baicalein, an antioxidant 12/15-lipoxygenase inhibitor improves clinical rating scores following multiple infarct embolic strokes. Neuroscience 2007 150 3 585 591 2-s2.0-36749068009 10.1016/j.neuroscience.2007.09.033
61. Kim S. W., Jin Y., Shin J. H., Kim I. D., Lee H. K., Park S., Han P. L., Lee J. K., Glycyrrhizic acid affords robust neuroprotection in the postischemic brain via anti-inflammatory effect by inhibiting HMGB1 phosphorylation and secretion. Neurobiology of Disease 2012 46 1 147 156
62. Kao T. K., Ou Y. C., Kuo J. S., Chen W. Y., Liao S. L., Wu C. W., Chen C. J., Ling N. N., Zhang Y. H., Peng W. H., Neuroprotection by tetramethylpyrazine against ischemic brain injury in rats. Neurochemistry International 2006 48 3 166 176 2-s2.0-30544445874 10.1016/j.neuint.2005.10.008
63. Liao S. L., Kao T. K., Chen W. Y., Lin Y. S., Chen S. Y., Raung S. L., Wu C. W., Lu H. C., Chen C. J., Tetramethylpyrazine reduces ischemic brain injury in rats. Neuroscience Letters 2004 372 1-2 40 45 2-s2.0-8644288259 10.1016/j.neulet.2004.09.013
64. Franke T. F., Hornik C. P., Segev L., Shostak G. A., Sugimoto C., PI3K/Akt and apoptosis: size matters. Oncogene 2003 22 56 8983 8998 2-s2.0-1642471831 10.1038/sj.onc.1207115
65. Scheid M. P., Marignani P. A., Woodgett J. R., Multiple phosphoinositide 3-kinase-dependent steps in activation of protein kinase B. Molecular and Cellular Biology 2002 22 17 6247 6260 2-s2.0-0036333737 10.1128/MCB.22.17.6247- 6260.2002
66. Vara J. Á. F., Casado E., de Castro J., Cejas P., Belda-Iniesta C., González-Barón M., P13K/Akt signalling pathway and cancer. Cancer Treatment Reviews 2004 30 2 193 204 2-s2.0-1642617693 10.1016/j.ctrv.2003.07.007
67. Omori N., Jin G., Li F., Zhang W. R., Wang S. J., Hamakawa Y., Nagano I., Manabe Y., Shoji M., Abe K., Enhanced phosphorylation of PTEN in rat brain after transient middle cerebral artery occlusion. Brain Research 2002 954 2 317 322 2-s2.0-0037044910 10.1016/S0006-8993(02)03366-8
68. Ning K., Pei L., Liao M., Liu B., Zhang Y., Jiang W., Mielke J. G., Li L., Chen Y., El-Hayek Y. H., Fehlings M. G., Zhang X., Liu F., Eubanks J., Wan Q., Dual neuroprotective signaling mediated by downregulating two distinct phosphatase activities of PTEN. Journal of Neuroscience 2004 24 16 4052 4060 2-s2.0-11144356390 10.1523/JNEUROSCI.5449-03.2004
69. Wu D. N., Pei D. S., Wang Q., Zhang G. Y., Down-regulation of PTEN by sodium orthovanadate inhibits ASK1 activation via PI3-K/Akt during cerebral ischemia in rat hippocampus. Neuroscience Letters 2006 404 1-2 98 102 2-s2.0-33745895330 10.1016/j.neulet.2006.05.018
70. Lee J. H., Kim K. Y., Lee Y. K., Park S. Y., Kim C. D., Lee W. S., Rhim B. Y., Hong K. W., Cilostazol prevents focal cerebral ischemic injury by enhancing casein kinase 2 phosphorylation and suppression of phosphatase and tensin homolog deleted from chromosome 10 phosphorylation in rats. Journal of Pharmacology and Experimental Therapeutics 2004 308 3 896 903 2-s2.0-1342302121 10.1124/jpet.103.061853
71. Franke T. F., Kaplan D. R., Cantley L. C., PI3K: downstream AKTion blocks apoptosis. Cell 1997 88 4 435 437 2-s2.0-0030907987 10.1016/S0092-8674(00) 81883-8
72. Fukunaga K., Kawano T., Akt is a molecular target for signal transduction therapy in brain ischemic insult. Journal of Pharmacological Sciences 2003 92 4 317 327 2-s2.0-0042734922
73. Pap M., Cooper G. M., Role of glycogen synthase kinase-3 in the phosphatidylinositol 3- kinase/Akt cell survival pathway. Journal of Biological Chemistry 1998 273 32 19929 19932 2-s2.0-0032493729 10.1074/jbc.273.32.19929
74. Bhat R. V., Shanley J., Correll M. P., Fieles W. E., Keith R. A., Scott C. W., Lee C. M., Regulation and localization of tyrosine216 phosphorylation of glycogen synthase kinase-3 β in cellular and animal models of neuronal degeneration. Proceedings of the National Academy of Sciences of the United States of America 2000 97 20 11074 11079 2-s2.0-0034718421
75. Zimmermann S., Moelling K., Phosphorylation and regulation of Raf by Akt (protein kinase B). Science 1999 286 5445 1741 1744 2-s2.0-0033607633 10.1126/science.286.5445.1741