Korean J Anat.  2003 Oct;36(5):343-352.

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

• Kim HJ
• Kim JM
• Chang N
• Park H
• Hann HJ
• Lee H

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.

Keyword

Homocysteine; folate; eNOS; NF-kappaB; Brain; Diet

MeSH Terms

Animals
Atherosclerosis
Blotting, Western
Brain
Cell Adhesion Molecules
Cell Proliferation
Diet
Folic Acid*
Homocysteine
Homocystine
Hyperhomocysteinemia*
Inflammation
NF-kappa B
Nitric Oxide
Nitric Oxide Synthase Type III*
Pathologic Processes
Plasma
Rats
Risk Factors
Stroke
Vascular Diseases
Cell Adhesion Molecules
Folic Acid
Homocysteine
Homocystine
NF-kappa B
Nitric Oxide
Nitric Oxide Synthase Type III