Complementary antioxidant defense by cytoplasmic and mitochondrial peroxiredoxins in Leishmania infantum

被引:77
作者
Castro, H
Sousa, C
Santos, M
Cordeiro-Da-Silva, A
Flohé, L
Tomás, AM
机构
[1] Inst Mol & Cell Biol, P-4150180 Oporto, Portugal
[2] Univ Porto, Fac Pharm, P-4100 Oporto, Portugal
[3] Tech Univ Braunschweig, Dept Biochem, D-3300 Braunschweig, Germany
[4] Univ Porto, Abel Salazar Inst Biomed Res, P-4100 Oporto, Portugal
关键词
peroxiredoxin; tryparedoxin peroxidase; antioxidant defense; cytoplasm; mitochondria; Leishmania infantum; free radicals;
D O I
10.1016/S0891-5849(02)01089-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In Kinetoplastida 2-Cys peroxiredoxins are the ultimate members of unique enzymatic cascades for detoxification of peroxides, which are dependent on trypanothione, a small thiol specific to these organisms. Here we report on two distinct Leishmania infantum peroxiredoxins, LicTXNPx and LimTXNPx, that may be involved in such a pathway. LicTXNPx, found in the cytoplasm, is a typical 2-Cys peroxiredoxin encoded by Lic7-XNPx, a member of a multicopy gene family. LimTXNPx, encoded by a single copy gene, Lim7XNPx, is confined to the mitochondrion and is unusual in possessing an Ile-Pro-Cys motif in the distal redox center, replacing the common peroxiredoxin Val-Cys-Pro sequence, apart from an N-terminal mitochondrial leader sequence. Based on sequence and subcellular localization, the peroxiredoxins of Kinetoplastida can be separated in two distinct subfamilies. As an approach to investigate the function of both peroxiredoxins in the cell, L. infantum promastigotes overexpressing LicTXNPx and LimTXNPx were assayed for their resistance to H2O2 and tert-butyl hydroperoxide. The results show evidence that both enzymes are active as peroxidases in vivo and that they have complementary roles in parasite protection against oxidative stress. (C) 2002 Elsevier Science Inc.
引用
收藏
页码:1552 / 1562
页数:11
相关论文
共 41 条
  • [1] The structure of reduced tryparedoxin peroxidase reveals a decamer and insight into reactivity of 2Cys-peroxiredoxins
    Alphey, MS
    Bond, CS
    Tetaud, E
    Fairlamb, AH
    Hunter, WN
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 2000, 300 (04) : 903 - 916
  • [2] Cloning and characterization of three differentially expressed peroxidoxin genes from Leishmania chagasi -: Evidence for an enzymatic detoxification of hydroxyl radicals
    Barr, SD
    Gedamu, L
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (36) : 34279 - 34287
  • [3] Beverley S M, 1993, Methods Mol Biol, V21, P333
  • [4] HYDROGEN-PEROXIDE GENERATION IN TRYPANOSOMA-CRUZI
    BOVERIS, A
    STOPPANI, AOM
    [J]. EXPERIENTIA, 1977, 33 (10): : 1306 - 1308
  • [5] PREDICTION AND IDENTIFICATION OF NEW NATURAL SUBSTRATES OF THE YEAST MITOCHONDRIAL INTERMEDIATE PEPTIDASE
    BRANDA, SS
    ISAYA, G
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (45) : 27366 - 27373
  • [6] Specificity and kinetics of a mitochondrial peroxiredoxin of Leishmania infantum
    Castro, H
    Budde, H
    Flohé, L
    Hofmann, B
    Lünsdorf, H
    Wissing, J
    Tomás, AM
    [J]. FREE RADICAL BIOLOGY AND MEDICINE, 2002, 33 (11) : 1563 - 1574
  • [7] CHAE HZ, 1994, J BIOL CHEM, V269, P27670
  • [8] SUCCINATE-DEPENDENT METABOLISM IN TRYPANOSOMA-CRUZI EPIMASTIGOTES
    DENICOLASEOANE, A
    RUBBO, H
    PRODANOV, E
    TURRENS, JF
    [J]. MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1992, 54 (01) : 43 - 50
  • [9] Glutathione and trypanothione in parasitic hydroperoxide metabolism
    Flohé, L
    Hecht, HJ
    Steinert, P
    [J]. FREE RADICAL BIOLOGY AND MEDICINE, 1999, 27 (9-10) : 966 - 984
  • [10] Tryparedoxin peroxidase of Leishmania donovani:: Molecular cloning, heterologous expression, specificity, and catalytic mechanism
    Flohé, L
    Budde, H
    Bruns, K
    Castro, H
    Clos, J
    Hofmann, B
    Kansal-Kalavar, S
    Krumme, D
    Menge, U
    Plank-Schumacher, K
    Sztajer, H
    Wissing, J
    Wylegalla, C
    Hecht, HJ
    [J]. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2002, 397 (02) : 324 - 335