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M94A2501.TXT
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1994-10-25
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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).