A high soy diet reduces programmed cell death and enhances bcl-xL expression in experimental stroke.
Soy phytoestrogens have been proposed as an alternative to estrogen replacement therapy and have demonstrated potential neuroprotective effects in the brain. We have shown that a high soy diet significantly reduces infarct size following permanent middle cerebral artery occlusion (MCAO). Here, we tested the hypothesis that a high soy diet would attenuate programmed cell death after stroke. Adult female Sprague-Dawley rats were ovariectomized and fed either an isoflavone-reduced diet (IFP) or a high soy diet (SP) for 2 weeks before undergoing 90 min of transient middle cerebral artery occlusion (tMCAO) followed by 22.5 h reperfusion. Infarct size, as assessed by triphenyltetrazolium chloride staining, was significantly reduced by a high soy diet (P<0.05). Apoptosis in the ischemic cortex, measured by TUNEL staining, was significantly reduced by the high soy diet. The number of active caspase-3 positive cells and caspase-mediated alpha-spectrin cleavage were also significantly decreased in the ischemic cortex of SP rats. Furthermore, nuclear translocation of apoptosis-inducing factor (AIF) was significantly reduced in the ischemic cortex of SP rats. Soy significantly increased bcl-x(L) mRNA and protein expression in the ischemic cortex compared with IFP rats. Immunohistochemistry revealed increased neuronal expression of bcl-2 and bcl-x(L) in the ischemic cortex of both IFP and SP rats following tMCAO. These results suggest that a high soy diet decreases both caspase-dependent and caspase-independent programmed cell death following tMCAO. Further, a high soy diet enhances expression of the cell survival factor bcl-x(L) following tMCAO, contributing to the neuroprotective effects of soy in the ischemic cortex.
Lovekamp-Swan
T
T
Department of Physiology, CA3145, Medical College of Georgia, 1120 15th Street, Augusta, GA 30912, USA.
Glendenning
M
M
Schreihofer
D A
DA
D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D051033:Apoptosis Inducing Factor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D020169:Caspases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D004967:Estrogens / Q000378:metabolism; D005260:Female; D005526:Food, Formulated; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D048789:Phytoestrogens / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D045730:Soy Foods; D020521:Stroke / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D051020:bcl-X Protein / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
C494831:Aifm1 protein, rat; D051033:Apoptosis Inducing Factor; D051017:Apoptosis Regulatory Proteins; C494813:Bcl2l1 protein, rat; D004967:Estrogens; D018696:Neuroprotective Agents; D048789:Phytoestrogens; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051020:bcl-X Protein; D020169:Caspases
Neuroreport. 1995 Oct 2;6(14):1917-21
8547598
Neurobiol Dis. 2006 Nov;24(2):345-56
16996745
Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6939-42
9192670
J Neurosci. 1998 Jul 1;18(13):4914-28
9634557
Hum Gene Ther. 2000 May 20;11(8):1123-37
10834615
FEBS Lett. 2000 Jul 7;476(3):118-23
10913597
Endocrinology. 2001 Mar;142(3):969-73
11181507
J Neurosci. 2001 Oct 1;21(19):7543-50
11567044
J Am Coll Nutr. 2001 Oct;20(5 Suppl):354S-362S; discussion 381S-383S
11603644
Obstet Gynecol. 2002 Jul;100(1):18-25
12100799
JAMA. 2002 Jul 17;288(3):321-33
12117397
J Neurochem. 2003 May;85(4):1026-36
12716434
J Neuropathol Exp Neurol. 2003 Apr;62(4):329-39
12722825
J Nutr. 2003 Jun;133(6):1983S-1986S
12771350
Trends Endocrinol Metab. 2003 Jul;14(5):228-35
12826329
Neuropathol Appl Neurobiol. 2003 Oct;29(5):472-81
14507339
J Cereb Blood Flow Metab. 2003 Oct;23(10):1137-50
14526224
J Cereb Blood Flow Metab. 1990 Mar;10(2):290-3
1689322
Neuropathol Appl Neurobiol. 1991 Feb;17(1):61-7
2057051
Proc Natl Acad Sci U S A. 1995 May 9;92(10):4304-8
7753802
Brain Res. 2003 Dec 12;993(1-2):10-7
14642826
J Neurosci. 2003 Dec 10;23(36):11420-6
14673006
Curr Med Chem. 2004 May;11(10):1333-43
15134523
J Cereb Blood Flow Metab. 2004 Jun;24(6):681-92
15181376
Stroke. 2004 Nov;35(11 Suppl 1):2644-7
15459443
Stroke. 1989 Jan;20(1):84-91
2643202
Biochem Biophys Res Commun. 1999 May 19;258(3):685-8
10329446
Neurosci Lett. 1999 Jun 25;268(3):119-22
10406019
J Neurosci. 1999 Aug 1;19(15):6385-93
10414967
Endocr Rev. 2005 May;26(3):308-12
15851820
Am J Physiol Regul Integr Comp Physiol. 2005 Jul;289(1):R103-8
15956759
Neuroscience. 2005;135(1):73-80
16111822
Eur J Neurosci. 2006 Feb;23(3):703-10
16487152
J Vet Med Sci. 2006 Mar;68(3):277-80
16598173
J Cereb Blood Flow Metab. 2006 May;26(5):708-21
16163298
Cerebrovasc Dis. 2006;21 Suppl 2:48-53
16651814
BMC Neurosci. 2006;7:49
16776830
Annu Rev Neurosci. 1997;20:245-67
9056714