Effects of Folate Supplementation on Cerebral Nuclear Factor-kappa B (NF-kappaB) and Endothelial Nitric Oxide Synthase Activities in Experimental Hyperhomocysteinemia / 대한해부학회지

ABSTRACT

Homocysteine is a significant but modifiable risk factor for vascular diseases, including stroke. While several pathological processes may be involved, homocysteine can cause significant endothelial impairment and compromise vascular nitric oxide (NO) bioactivity. Endothelial dysfunction can be characterized not only by impaired vasoreactivity with decreased availability of NO but also abnormal inflammatory cell-endothelial interactions and increased expression of cell adhesion molecules. Nuclear factor-kappa B (NF-kappaB) is a transcriptional factor which plays a coordinating role in inflammation and cellular proliferation and may be involved in early atherosclerosis. Experimentally, we investigated the effects of folate supplementation on endothelial nitric oxide synthase (eNOS) activity in the hyperhomocysteinemic rat brain and related the changes of eNOS activity to the expression of NF-kappaB. Animals were raised on an experimental diet containing 0.3% homocystine for 4 weeks or on a 0.3% homocystine diet for 2 weeks with or without folate supplementation (8 mg/kg diet). The cerebrovascular endothelial nitric oxide synthase (eNOS) activity was investigated by the immunohistochemical method. Cerebral contents of eNOS and NF-kappaB were also evaluated with the western blot analysis. At 4 wks, diet- induced hyperhomocysteinemia up to 4-fold (control: 6.5+/-0.4 micromol/L, homocystine: 26.2+/-2.5 micromol/L), and a reduction in the expression of cerebral eNOS with a concomitant increase in NF-kappaB. Dietary folate supplementation caused a significant decrease in plasma homocysteine levels with a concomitant increase in hyperhomocysyeinemia-induced reduction of the cerebral eNOS and decrease in hyperhomocysyeinemia-induced NF-kappaB expression.