Alpha-tocopherol transfer protein disruption confers resistance to malarial infection in mice

作者：Herbas Maria S; Ueta Yoshiko Y; Ichikawa Chie; Chiba Mayumi; Ishibashi Kana; Shichiri Mototada; Fukumoto Shinya; Yokoyama Naoaki; Takeya Motohiro; Xuan Xuenan; Arai Hiroyuki; Suzuki Hiroshi^*

来源：Malaria Journal, 2010, 9: 101.

DOI：10.1186/1475-2875-9-101

Background: Various factors impact the severity of malaria, including the nutritional status of the host. Vitamin E, an intra and extracellular anti-oxidant, is one such nutrient whose absence was shown previously to negatively affect Plasmodium development. However, mechanisms of this Plasmodium inhibition, in addition to means by which to exploit this finding as a therapeutic strategy, remain unclear.
Methods: alpha-TTP knockout mice were infected with Plasmodium berghei NK65 or Plasmodium yoelii XL-17, parasitaemia, survival rate were monitored. In one part of the experiments mice were fed with a supplemented diet of vitamin E and then infected. In addition, parasite DNA damage was monitored by means of comet assay and 8-OHdG test. Moreover, infected mice were treated with chloroquine and parasitaemia and survival rate were monitored.
Results: Inhibition of a-tocopherol transfer protein (alpha-TTP), a determinant of vitamin E concentration in circulation, confers resistance to malarial infection as a result of oxidative damage to the parasites. Furthermore, in combination with the anti-malarial drug chloroquine results were even more dramatic.
Conclusion: Considering that these knockout mice lack observable negative impacts typical of vitamin E deficiency, these results suggest that inhibition of alpha-TTP activity in the liver may be a useful strategy in the prevention and treatment of malaria infection. Moreover, a combined strategy of alpha-TTP inhibition and chloroquine treatment might be effective against drug resistant parasites.

• 出版日期2010-4-19