Intracellular fragmentation of bone resorption products by reactive oxygen species generated by osteoclastic tartrate-resistant acid phosphatase

被引:191
作者
Halleen, JM
Räisänen, S
Salo, JJ
Reddy, SV
Roodman, GD
Hentunen, TA
Lehenkari, PP
Kaija, H
Vihko, P
Väänänen, HK [1 ]
机构
[1] Univ Turku, Inst Biomed, Dept Anat, FIN-20520 Turku, Finland
[2] Univ Helsinki, Cent Hosp, Dept Orthopaed & Traumatol, FIN-02260 Helsinki, Finland
[3] Univ Texas, Hlth Sci Ctr, Dept Med & Hematol, San Antonio, TX 78284 USA
[4] Rayne Inst, Bone & Mineral Ctr, London WC1E 6JJ, England
[5] Univ Oulu, Collaborating Ctr Res Reprod Hlth, FIN-90220 Oulu, Finland
[6] Univ Oulu, Bioctr Oulu, FIN-90220 Oulu, Finland
[7] Univ Helsinki, Dept Biosci, FIN-00014 Helsinki, Finland
关键词
D O I
10.1074/jbc.274.33.22907
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
Tartrate-resistant acid phosphatase (TRAP) is highly expressed in bone-resorbing osteoclasts and activated macrophages, It has been suggested that a redox-active iron in the binuclear iron center of TRAP could have the capacity to react with hydrogen peroxide to produce highly destructive reactive oxygen species (ROS), Here we show that TRAP can generate ROS in vitro and that cells over-expressing TRAP produce higher amounts of intracellular ROS than their parent cells. We further demonstrate that these ROS can be targeted to destroy collagen and other proteins. In resorbing osteoclasts, TRAP was found in transcytotic vesicles transporting matrix degradation products through the cell, suggesting that TRAP-facilitated fragmentation of endocytosed material takes place in a specific cellular compartment. These results suggest that bone matrix degradation occurs not only extracellularly in the resorption lacunae but also intracellularly in the transcytotic vesicles. We propose that proteins containing redox-active iron could represent a novel mechanism of physiological fragmentation of organic molecules. This mechanism could be important in tissue remodeling and as a defense mechanism of phagocytosing cells.
引用
收藏
页码:22907 / 22910
页数:4
相关论文
共 31 条
[1]  
[Anonymous], PRINCIPLES BONE BIOL
[2]   POLARIZED SECRETION OF LYSOSOMAL-ENZYMES - CO-DISTRIBUTION OF CATION-INDEPENDENT MANNOSE-6-PHOSPHATE RECEPTORS AND LYSOSOMAL-ENZYMES ALONG THE OSTEOCLAST EXOCYTIC PATHWAY [J].
BARON, R ;
NEFF, L ;
BROWN, W ;
COURTOY, PJ ;
LOUVARD, D ;
FARQUHAR, MG .
JOURNAL OF CELL BIOLOGY, 1988, 106 (06) :1863-1872
[3]   Protein oxidation in aging, disease, and oxidative stress [J].
Berlett, BS ;
Stadtman, ER .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (33) :20313-20316
[4]   OSTEOCLASTIC BONE-RESORPTION BY A POLARIZED VACUOLAR PROTON PUMP [J].
BLAIR, HC ;
TEITELBAUM, SL ;
GHISELLI, R ;
GLUCK, S .
SCIENCE, 1989, 245 (4920) :855-857
[5]   ISOLATED OSTEOCLASTS RESORB THE ORGANIC AND INORGANIC COMPONENTS OF BONE [J].
BLAIR, HC ;
KAHN, AJ ;
CROUCH, EC ;
JEFFREY, JJ ;
TEITELBAUM, SL .
JOURNAL OF CELL BIOLOGY, 1986, 102 (04) :1164-1172
[6]  
CLARK SA, 1989, J BONE MINER RES, V4, P399
[7]  
DAVIES KJA, 1987, J BIOL CHEM, V262, P9908
[8]   EVIDENCE FOR A SPIN-COUPLED BINUCLEAR IRON UNIT AT THE ACTIVE-SITE OF THE PURPLE ACID-PHOSPHATASE FROM BEEF SPLEEN [J].
DAVIS, JC ;
AVERILL, BA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1982, 79 (15) :4623-4627
[9]  
Doi K., 2005, BIOINORG CHEM, P1
[10]  
Garnero Patrick, 1996, P1277