Document 2501
 DOCN  M94A2501
 TI    Role of ADF/human thioredoxin in cystine transport: possible application
       of ADF/thioredoxin and NAC in AIDS.
 DT    9412
 AU    Iwata S; Hori T; Sato N; Masutani H; Mitui A; Nakamura K; Yodoi J; Dept.
       of Biological Responses, Kyoto Univ., Japan.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):29 (abstract no. 089A). Unique
       Identifier : AIDSLINE ICA10/94370074
 AB    OBJECTIVE: In AIDS or ARC patients, reduction of acid-soluble thiols
       (GSH or L-cysteine) has been shown in their PBMC or serum and related to
       the decrease and dysfunction of lymphocytes which might cause the
       immunodeficiency. The loss of ADF high producer cells has also been
       reported in the thymus and lymph nodes of AIDS patients, indicating a
       possible involvement of ADF in their immunodeficiency. METHODS:
       L-cystine transport activity of PBL-blasts was evaluated by measurement
       of radioactivity of 14C-L-cystine incorporated into the cells. GSH
       content was determined by enzymatic recycling assay. Apoptosis caused by
       thiol deficiency was analyzed by flow cytometry and electrophoresis.
       RESULTS: Adult T cell leukemia-derived factor (ADF)/human thioredoxin
       enhanced the cystine transport of PBL blasts in a dose dependent manner
       and synergistically with NAC. The GSH reduction in PBL-blasts caused by
       L-cystine deficiency was also dose-dependently restored by addition of
       rADF. Furthermore, the various T-cell lines such as MT-2, ATL-2 were led
       to the apoptotic cell death by thiol depletion, which was partially
       rescued by addition of rADF. DISCUSSION AND CONCLUSIONS: There have been
       accumulating evidences that oxidative stress-induced apoptosis may play
       important roles in pathogenesis in immunodeficiency in AIDS patients.
       Our results imply the interaction between ADF/human thioredoxin system
       and GSH system, because L-cystine and NAC are precursors of GSH.
       Apoptosis caused by thiol-depletion might reflect the loss of
       lymphocytes in AIDS and ARC patients whose serum thiol level was
       reported to be low.
 DE    Acquired Immunodeficiency Syndrome/*METABOLISM  Apoptosis  Biological
       Transport  Cell Line  Cells, Cultured  Cystine/*METABOLISM
       Dose-Response Relationship, Drug  DNA-Binding Proteins  Flow Cytometry
       Human  Neoplasm Proteins/*PHARMACOLOGY  Sulfhydryl Compounds/METABOLISM
       T-Lymphocytes  Thioredoxin/*PHARMACOLOGY  Transcription Factors  MEETING
       ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).