Sulfur Metabolism in AIDS: Cystamine as an Anti-HIV Agent

被引:13
作者
Toohey, John I. [1 ]
机构
[1] Cytoregulat Res, Elgin, ON K0G 1E0, Canada
关键词
CYSTATHIONINE GAMMA-LYASE; IN-VITRO; CELLS; REPLICATION; LYMPHOCYTES; CYSTEINE; RAT; CYSTINE; LIVER; DEFICIENCY;
D O I
10.1089/aid.2009.0091
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Numerous reports have documented disturbances of sulfur metabolism in AIDS patients. There is a generalized loss of sulfur from the body, measured as cysteine and glutathione. The enzyme, cystathionase, has been shown to be greatly decreased in the liver of AIDS patients. Cystathionase is known to catalyze beta elimination of cystine giving rise to sulfane sulphur, which has potent stimulatory properties for lymphocytes. When both cystine and cystathionase are deficient in AIDS, the lymphocytes would lack this important regulator, which might be replenished by giving cystamine. Cystamine is a small disulfide that gives rise to sulfane sulfur when it undergoes oxidation catalyzed by diamine oxidase (a ubiquitous enzyme in animals). Cystamine has been shown to cause marked suppression of HIV replication in cultured lymphocytes and macrophages; the inference is that the cystamine/diamine oxidase system may replace the cystine/cystathionase system as a source of sulfane sulfur. Sulfane sulfur could have two beneficial effects: (1) it could increase the vigor and resistance of the lymphocyes and (2) it could interfere with the HIV replication process. A clinical trial of cystamine in AIDS is indicated.
引用
收藏
页码:1057 / 1060
页数:4
相关论文
共 36 条
[21]   ORGANIC THIOPHOSPHATE WR-151327 SUPPRESSES EXPRESSION OF HIV IN CHRONICALLY INFECTED-CELLS [J].
KALEBIC, T ;
SCHEIN, PS .
AIDS RESEARCH AND HUMAN RETROVIRUSES, 1994, 10 (06) :727-733
[22]   Metalloenzyme nitrile hydratase: Structure, regulation, and application to biotechnology [J].
Kobayashi, M ;
Shimizu, S .
NATURE BIOTECHNOLOGY, 1998, 16 (08) :733-736
[23]   ACCUMULATION OF CYSTINE AUXOTROPHIC THYMOCYTES ACCOMPANYING TYPE-C VIRAL LEUKEMOGENESIS IN MOUSE [J].
LIVINGSTON, DM ;
FERGUSON, C ;
GOLLOGLY, R ;
LAZARUS, H .
CELL, 1976, 7 (01) :41-47
[24]   Hepatic γ-cystathionase deficiency in patients with AIDS [J].
Martin, JA ;
Sastre, J ;
de la Asunción, JG ;
Pallardó, FV ;
Viña, J .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2001, 285 (11) :1444-1445
[25]  
METCALF D, 1976, J IMMUNOL, V116, P635
[26]   BETA-CYANOALANINE AN INHIBITOR OF RAT LIVER CYSTATHIONASE [J].
PFEFFER, M ;
RESSLER, C .
BIOCHEMICAL PHARMACOLOGY, 1967, 16 (12) :2299-&
[27]   CHARACTERIZATION OF THE ENZYMIC CAPACITY FOR CYSTEINE DESULFHYDRATION IN LIVER AND KIDNEY OF THE RAT [J].
STIPANUK, MH ;
BECK, PW .
BIOCHEMICAL JOURNAL, 1982, 206 (02) :267-277
[28]  
TERESACO.M, 1972, ENZYMOLOGIA, V43, P271
[30]   PERSULFIDE SULFUR IS A GROWTH-FACTOR FOR CELLS DEFECTIVE IN SULFUR METABOLISM [J].
TOOHEY, JI .
BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE, 1986, 64 (08) :758-765