[Folic acid prevents Bcl-2 hypomethylation in rats with hyperhomocysteinemia].

OBJECTIVE

To investigate the effects of folic acid on Bcl-2 gene methylation status in rats with hyperhomocystinemia induced by ingestion of excess methionine.

METHODS

36 healthy 6-week-old wistar male rats, weighing (160 +/- 10) g, after being fed adaptable for one week, were randomly divided into control group (n = 12), hyperhomocysteinemia group (n = 12), folic acid treatment group (n = 12). The control group was fed with AIN-93G diet. The hyperhomocysteinemia group was fed with high-methionion diet, consisting of AIN-93G diet plus 1.7% methionion. The folic acid treatment group was fed with high-methionion plus folic acid-rich diet, consisting of AIN-93G diet plus 1.7% methionion and 0.008% folic acid. After be maintained for 18 weeks on the previously described diets, the concentrations in the plasma Hcy and folic acid and Vit B12 were measured with the IMX assays. The thoracic aorta was harvested for immunohist Chemical analysis. The methylation status of Bcl-2 gene was determined by nest touch-down PCR combined MSP(methylation specific PCR). Real-time RT PCR was used to detect mRNA expression of arotic Bcl-2.

RESULTS

The study showed the following: (a) A high methionine diet for 18 weeks is sufficient to induce hyperhom degree Cystinemia; Folic acid supplementation to the rats fed the high-methionine diet prevented an elevation homocysteine (Hcy) levels in the plasma (P < 0.01 ). (b) Compared with the control group, the Hhcy group had a elevating Bcl-2 expression by immunohistochemical analysis in aorta, along with Bcl-2 hypomethylation (P < 0.05) and increased Bcl-2 mRNA expression (P < 0.05 ). (c) Most important, after folic acid supplementation, the lowering of Hcy levels was accompanied by a marked decreased Bcl-2 expression by immunohistochemical analysis and Bcl-2 hypermethylation (P < 0.05) and reduced Bcl-2 mRNA expression (P < 0.05).

CONCLUSIONS

Folic acid supplementation can prevents Bcl-2 hypomethylation in rats with hyperhomocysteinemia, resulting in a decreased Bcl-2 expression.