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Downregulation of ADF/human thioredoxin as a possible mediator of HIV-induced apoptosis.

Sato N, Iwata S, Masutani H, Nakamura K, Hori T, Yodoi J; International Conference on AIDS.

Int Conf AIDS. 1994 Aug 7-12; 10: 95 (abstract no. PA0262).

Dept. of Biological Responses, Kyoto Univ., Japan.

OBJECTIVE: Recent evidence suggests that oxidative stress may mediates HIV-induced apoptosis of lymphocytes. We have previously shown that ADF/human thioredoxin (hTrx), an endogenous antioxidant, was downregulated by HIV infection. To study the possible involvement of ADF/thioredoxin in apoptotic process, we have analyzed the effect of thiol modification on a human T lymphoid cell line. METHODS: A human T lymphoid cell line, Jurkat, were treated with either diamide (a sulfhydryl-specific oxidant) or buthionine sulfoximine (BSO; an inhibitor of glutathione synthesis). After drug treatment, we have analyzed 1) intracellular GSH content by calorimetric assay, 2) oxidation state of ADF/hTrx by native-PAGE/immunoblotting, 3) DNA content after detergent extraction by propidium iodide staining/flowcytometry. RESULTS: When cells were treated with diamide, decrease of GSH content, oxidation of ADF/hTrx and induction of apoptosis were observed, whereas the treatment with BSO did not induce apoptosis or oxidation of ADF/hTrx up to 48 hours in spite of marked decrease of GSH content. DISCUSSION AND CONCLUSIONS: Our results implies that oxidation or inactivation of ADF/hTrx may lead to apoptotic cell death. The downregulation of ADF/hTrx may have pathogenic or facilitatory roles in HIV-induced apoptosis. Whether replenishment of ADF/hTrx blocks HIV-induced apoptosis remains to be determined to establish the therapeutic potential of ADF/hTrx for HIV infection.

Publication Types:
  • Meeting Abstracts
Keywords:
  • AIDS Vaccines
  • Apoptosis
  • Buthionine Sulfoximine
  • CASP4 protein, human
  • Caspases
  • Cell Death
  • Cytokines
  • Diamide
  • Down-Regulation
  • Fungal Proteins
  • Glutathione
  • Humans
  • Lymphocytes
  • Neoplasm Proteins
  • Oxidants
  • Oxidation-Reduction
  • Oxidoreductases
  • Sulfhydryl Compounds
  • Thioredoxins
  • adult T cell leukemia-derived factor
  • genetics
Other ID:
  • 94372555
UI: 102211388

From Meeting Abstracts




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