title: A high soy diet reduces programmed cell death and enhances bcl-xL expression in experimental stroke.
abstract: 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.
authors: Department of Physiology, CA3145, Medical College of Georgia, 1120 15th Street, Augusta, GA 30912, USA.
authors: T
authors: T
authors: Lovekamp-Swan
authors: M
authors: M
authors: Glendenning
authors: D A
authors: DA
authors: Schreihofer
mesh_terms: 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
chemical_list: 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
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