title: Alpha-tocopherol transfer protein disruption confers resistance to malarial infection in mice.
abstract: 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 alpha-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Research Unit for Functional Genomics, National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Nishi 2-13, Inada, Obihiro, 080-8555 Japan.
authors.forename: Maria S
authors.initials: MS
authors.lastname: Herbas
authors.forename: Yoshiko Y
authors.initials: YY
authors.lastname: Ueta
authors.forename: Chie
authors.initials: C
authors.lastname: Ichikawa
authors.forename: Mayumi
authors.initials: M
authors.lastname: Chiba
authors.forename: Kana
authors.initials: K
authors.lastname: Ishibashi
authors.forename: Mototada
authors.initials: M
authors.lastname: Shichiri
authors.forename: Shinya
authors.initials: S
authors.lastname: Fukumoto
authors.forename: Naoaki
authors.initials: N
authors.lastname: Yokoyama
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
authors.forename: Xuenan
authors.initials: X
authors.lastname: Xuan
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002738:Chloroquine / Q000627:therapeutic use; D007113:Immunity, Innate; D008288:Malaria / Q000469:parasitology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress; D018512:Parasitemia / Q000188:drug therapy; D010962:Plasmodium berghei / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D010967:Plasmodium yoelii / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development*; D015996:Survival Rate; D014810:Vitamin E / Q000008:administration & dosage / Q000378:metabolism; D014811:Vitamin E Deficiency; D014815:Vitamins / Q000008:administration & dosage / Q000378:metabolism
chemical_list: D000962:Antimalarials; D002352:Carrier Proteins; D014815:Vitamins; C017763:alpha-tocopherol transfer protein; D014810:Vitamin E; D002738:Chloroquine
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