ASCORBIC-ACID ENHANCES FERRITIN MESSENGER-RNA TRANSLATION BY AN IRP/ACONITASE SWITCH

被引:56
作者
TOTH, I [1 ]
BRIDGES, KR [1 ]
机构
[1] HARVARD UNIV, BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED, DIV HEMATOL ONCOL, BOSTON, MA 02115 USA
关键词
D O I
10.1074/jbc.270.33.19540
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
Replenishment of ascorbate in cultured cells, which are almost uniformly vitamin-deficient, increases ferritin mRNA translation in response to iron by 20-fold (Toth, I., Rogers, J. T., McPhee, J. A., Elliott, S, M., Abramson, S. L., and Bridges, K. R. (1995) J. Biol, Chem. 270, 2846-2852). We now demonstrate that ascorbate increases cytosolic aconitase activity. The iron-responsive element-binding protein (IRP-1) exists in three states: bound to mRNA without aconitase activity, free in the cytosol without aconitase activity, and free in the cytosol with aconitase activity. Ascorbate converts free IRP-1 to the enzymatically active form. Enhanced ferritin synthesis with subsequent iron stimulation is due to the altered equilibrium of the free IRP-1. The cellular biology of iron is closely intertwined with that of ascorbate.
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收藏
页码:19540 / 19544
页数:5
相关论文
共 36 条
[1]   THE IRON-RESPONSIVE ELEMENT-BINDING PROTEIN - LOCALIZATION OF THE RNA-BINDING SITE TO THE ACONITASE ACTIVE-SITE CLEFT [J].
BASILION, JP ;
ROUAULT, TA ;
MASSINOPLE, CM ;
KLAUSNER, RD ;
BURGESS, WH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (02) :574-578
[2]  
BRIDGES KR, 1986, J BIOL CHEM, V261, P14273
[3]  
BRIDGES KR, 1987, J BIOL CHEM, V262, P14773
[4]   MISSING STEP IN MAN, MONKEY AND GUINEA PIG REQUIRED FOR THE BIOSYNTHESIS OF L-ASCORBIC ACID [J].
BURNS, JJ .
NATURE, 1957, 180 (4585) :552-552
[5]   MODULATION OF THE RNA-BINDING ACTIVITY OF A REGULATORY PROTEIN BY IRON INVITRO - SWITCHING BETWEEN ENZYMATIC AND GENETIC FUNCTION [J].
CONSTABLE, A ;
QUICK, S ;
GRAY, NK ;
HENTZE, MW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (10) :4554-4558
[6]   IRON REGULATORY FACTOR EXPRESSED FROM RECOMBINANT BACULOVIRUS - CONVERSION BETWEEN THE RNA-BINDING APOPROTEIN AND FE-S CLUSTER CONTAINING ACONITASE [J].
EMERYGOODMAN, A ;
HIRLING, H ;
SCARPELLINO, L ;
HENDERSON, B ;
KUHN, LC .
NUCLEIC ACIDS RESEARCH, 1993, 21 (06) :1457-1461
[7]   THE BIOCHEMICAL FUNCTIONS OF ASCORBIC-ACID [J].
ENGLARD, S ;
SEIFTER, S .
ANNUAL REVIEW OF NUTRITION, 1986, 6 :365-406
[8]   ANTIOXIDANT DEFENSES AND LIPID-PEROXIDATION IN HUMAN-BLOOD PLASMA [J].
FREI, B ;
STOCKER, R ;
AMES, BN .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (24) :9748-9752
[9]  
GARDNER PR, 1992, J BIOL CHEM, V267, P8757
[10]   EFFECT OF GLUTATHIONE ON ACONITASE IN ESCHERICHIA-COLI [J].
GARDNER, PR ;
FRIDOVICH, I .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1993, 301 (01) :98-102