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Sulfation of nitrotyrosine: Role of the human cytosolic SULT1A3
Author(s) -
Yasuda Shin,
Idell Steven,
Suiko Masahito,
Sakakibara Yoichi,
Liu MingCheh
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb28-a
Subject(s) - nitrotyrosine , sulfation , peroxynitrite , chemistry , cytosol , biochemistry , sulfotransferase , tyrosine , biophysics , enzyme , superoxide , biology , nitric oxide synthase
In addition to serving as a biomarker of oxidative/nitrative stress, elevated levels of nitrotyrosine have been shown to cause DNA damage or trigger apoptosis. The present study was designed to investigate the possibility that sulfation serves as a pathway for the inactivation/disposal of potentially harmful nitrotyrosine. Using metabolic labeling, nitrotyrosine O‐[35S]sulfate was found to be produced and released into the medium by HepG2 human hepatoma cells labeled with [35S]sulfate upon stimulation by 3‐morpholinosydnonimine (SIN‐1), a peroxynitrite generator. Of the eleven known human cytosolic sulfotransferases (SULTs), only SULT1A3 was found to be capable of sulfating nitrotyrosine. The pH‐dependence and kinetic constants of SULT1A3 with nitrotyrosine and dopamine as substrate were determined. In a time course study using [3H]tyrosine‐labeled HepG2 cells treated with SIN‐1, the bulk of free [3H]nitrotyrosine inside the cells was present in the unconjugated form. The proportion of sulfated [3H]nitrotyrosine increased dramatically in the medium over time. Furthermore, siRNA experiments have been carried out to verify the role of SULT1A3 in nitrotyrosine sulfation. The information obtained provides insight into the physiological relevance of the sulfation of nitrotyrosine.