Folate status affects tissue L-isoaspartate contents and immune responses in autoimmune mice

• Main Authors: Ying-Chu Chen, 陳盈竹
• Other Authors: Bi-Fong Lin
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/36566493461583711320

碩士 === 國立臺灣大學 === 微生物與生化學研究所 === 92 === Abstract Self-proteins undergo spontaneous posttranslational modifications, such as isoaspartyl form (IsoAsp), may alter the protein function, activity and alter the maintenance of peripheral immune tolerance. The enzyme protein L-isoaspartyl methyltransferase (PIMT) is involved in the repair of various proteins and folate may act as a cofactor to help repair IsoAsp site. This study investigated the effect of folate status and L-isoaspartate accumulation on autoimmune-prone mice and BALB/c mice. In exp1, ten-week-old female NZB/W F1 and BALB/c mice were divided into four groups fed an AIN 76-based diet containing either 0 (FD), 2 (F1), 4 (F2), or 10 (F5) mg folic acid/kg diet for 5 months. In exp2, six-week-old female MRL/lpr mice and BALB/c mice were divided into four groups fed an AIN 76-based diet containing either 0 (FD), 2 (F1), 10 (F5), or 20 (F10) mg folic acid/kg diet for 10 weeks to investigate the effects of dietary folate. The results showed that the folate concentrations in plasma, RBC, liver, and kidney significantly increased with increment of dietary folate, but no changes in brain and spleen. Supplementation with folate was found to have a preventive effect on the elevation of the TBARS values in tissues. In exp1 and exp2, we found that folate supplementation did not eliminate IsoAsp contents in mice. In exp1, the isoAsp content of NZB/W F1 mice accumulated with folate supplementation significantly in spleen, and isoAsp content in kidney was positive correlation with proteinuria (p=0.0436). IsoAsp content in kidney was positive correlation with anti-ds DNA autoantibodies and anti-ss DNA autoantibodies (p=0.0137; p=0.0472) when FD group was excluded. In exp2, the isoAsp content of MRL/lpr mice accumulated significantly in kidney, and folate concentration in plasma was positive correlation with anti-ds DNA autoantibodies (p=0.0308), and positive correlation with isoAsp content in kidney (p<0.0001) when FD group was excluded. In addition, autoimmune-prone mice fed folate supplement diet increased B cell proliferation, autoantibodies production, had higher PGE2 and enhanced lupus nephritis. The levels of isoAsp contents were higher in the older mice. Folate supplementation increased IsoAsp accumulation and may aggravate autoimmune disease. The mice fed folate deficient diet also had higher IsoAsp contents but lower immune response which may benefit autoimmune progress and had longer lifespan compared to the folate supplement group. Further studies are needed to clarify the mechanisms how folate supplementation increased isoAsp contents in both autoimmune and normal mice.