Nitration of specific tyrosines in FoF1ATP synthase and activity loss in aging

American Journal of Physiology - Endocrinology and Metabolism - Tập 298 Số 5 - Trang E978-E987 - 2010
Virginia Haynes1, Nathaniel J. Traaseth2, Sarah Elfering2,3, Yasuko Fujisawa4, Cecilia Giulivi4
1University of California, Davis, Department of Molecular Biosciences, 1120 Haring Hall, One Shields Ave., Davis, CA 95616, USA.
2Department of Biochemistry and Chemistry, University of Minnesota, Duluth, Minnesota
3Medicine - Renal and Hypertension Division
4Department of Molecular Biosciences, University of California, Davis, California; and

Tóm tắt

It has been reported that C-nitration of proteins occurs under nitrative/oxidative stress; however, its role in pathophysiological situations is not fully understood. In this study, we determined that nitration of Tyr345and Tyr368in the β-subunit of the mitochondrial FoF1-ATPase is a major target for nitrative stress in rat liver under in vivo conditions. The chemical characteristics of these Tyr make them suitable for a facilitated nitration (solvent accessibility, consensus sequence, and p Ka). Moreover, β-subunit nitration increased significantly with the age of the rats (from 4 to 80 weeks old) and correlated with decreased ATP hydrolysis and synthesis rates. Although its affinity for ATP binding was unchanged, maximal ATPase activity decreased between young and old rats by a factor of two. These changes directly impacted the available ATP concentration in vivo, and it was expected that they would affect multiple cellular ATP-dependent processes. For instance, at least 50% of available [ATP] in the liver of older rats would have to be committed to sustain maximal Na+-K+-ATPase activity, whereas only 30% would be required for young rats. If this requirement was not fulfilled, the osmoregulation and Na+-nutrient cotransport in liver of older rats would be compromised. On the basis of our studies, we propose that targeted nitration of the β-subunit is an early marker for nitrative stress and aging.

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Tài liệu tham khảo

10.1021/pr900039c

10.1038/370621a0

10.1196/annals.1297.060

10.1152/ajprenal.00330.2001

10.1016/j.cell.2005.02.001

10.1152/ajpcell.1996.271.5.C1424

10.1016/S1567-7249(01)00005-8

10.1016/0003-9861(83)90592-1

Brot N, 1991, Biofactors, 3, 91

Bullough DA, 1986, J Biol Chem, 261, 14171, 10.1016/S0021-9258(18)66999-6

Bullough DA, 1986, J Biol Chem, 261, 5722, 10.1016/S0021-9258(17)38442-9

Bullough DA, 1988, J Biol Chem, 263, 14053, 10.1016/S0021-9258(18)68183-9

10.1042/CS20080253

10.1016/j.mam.2004.02.005

Catterall WA, 1971, J Biol Chem, 246, 4987, 10.1016/S0021-9258(18)61961-1

10.1016/0076-6879(79)55039-3

Chance B, 1956, Adv Enzymol Relat Subj Biochem, 17, 65

10.1152/ajpcell.00310.2006

10.1007/BF00762200

10.1073/pnas.84.16.5715

Cross RL, 1982, J Biol Chem, 257, 2874, 10.1016/S0021-9258(19)81045-1

Davies KJ, 1987, J Biol Chem, 262, 9902, 10.1016/S0021-9258(18)48019-2

10.1212/01.wnl.0000192308.43151.63

10.1016/0005-2728(77)90093-7

10.1152/ajpheart.00766.2003

10.1038/216071a0

10.1042/BJ20090594

Galeotti T, 1976, Cancer Res, 36, 4175

10.1042/bj3320673

10.1152/ajpcell.00307.2006

10.1074/jbc.273.18.11038

10.1152/ajplung.2000.278.5.L961

10.1016/S0047-6374(98)00133-X

10.1007/BF00743212

10.1073/pnas.94.7.3064

10.1080/10715769900301221

10.1073/pnas.1131756100

10.1006/abbi.1998.0755

10.1016/0003-9861(92)90431-U

10.1016/j.febslet.2008.07.042

10.1016/S0304-3940(01)01576-2

10.1016/0022-2836(82)90515-0

10.1002/pmic.200800546

10.1055/s-2001-15413

Lowry OH, 1951, J Biol Chem, 193, 265, 10.1016/S0021-9258(19)52451-6

10.1038/nrm762

Nair KS, 2000, Mayo Clin Proc, 75, S14, 10.1016/S0025-6196(19)30636-6

Nalin CM, 1982, J Biol Chem, 257, 8055, 10.1016/S0021-9258(18)34296-0

10.1152/ajpcell.00213.2006

10.1196/annals.1404.015

Okamoto H, 1977, J Biol Chem, 252, 6125, 10.1016/S0021-9258(17)40039-1

10.1016/j.bbapap.2004.11.003

10.1002/elps.11501601187

10.1002/elps.11501601299

Pedersen PL, 1978, J Biol Chem, 253, 2176, 10.1016/S0021-9258(17)38056-0

10.1016/0076-6879(79)55081-2

Pedersen PL, 1981, J Biol Chem, 256, 1362, 10.1016/S0021-9258(19)69973-4

Pullman ME, 1963, J Biol Chem, 238, 3762, 10.1016/S0021-9258(19)75338-1

10.1126/science.123.3208.1105

Racker E, 1967, J Biol Chem, 242, 2547, 10.1016/S0021-9258(18)95998-3

10.1023/A:1022473219044

10.1083/jcb.38.1.158

10.1007/s10495-006-5881-9

10.1021/bi7009713

10.1016/j.cbpb.2005.05.004

10.1023/A:1015916831583

10.1016/S1044-0305(00)00219-1

10.1021/bi981295k

Thayer WS, 1979, J Biol Chem, 254, 7717, 10.1016/S0021-9258(18)36005-8

10.1016/0047-6374(91)90083-C

10.1016/0005-2728(76)90105-5

10.1146/annurev.genet.39.110304.095751