Document Detail

Involvement of SULT1A3 in elevated sulfation of 4-hydroxypropranolol in Hep G2 cells pretreated with beta-naphthoflavone.
MedLine Citation:
PMID:  15748705     Owner:  NLM     Status:  MEDLINE    
Pretreatment of Hep G2 cells with beta-naphthoflavone (BNF 1-25microM) significantly increased cytosolic sulfation activities of 4-hydroxypropranolol (4-OH-PL) racemate. The profile was similar to those of sulfations towards dopamine and triiodothyronine in the same cytosolic fractions. Kinetic studies of 4-OH-PL sulfation in Hep G2 cytosolic fractions revealed that V(max) values increased but apparent K(m) values remained unchanged following the BNF pretreatment. Among five recombinant human SULT isoforms (SULT1A1, -1A3, -1B1, -1E1 and -2A1) examined, only SULT2A1 did not show 4-OH-PL sulfation activities under the conditions used. SULT1A3 and -1E1 exhibited an enantioselectivity of 4-OH-R-PL sulfation>4-OH-S-PL sulfation, which agreed with that of BNF-pretreated Hep G2 cells as well as of nontreated cells, whereas SULT1A1 and -1B1 showed a reversed enantioselectivity (R<S). In kinetic studies of 4-OH-PL sulfations by four kinds of human SULT isoforms, apparent K(m) values for SULT1A3 were the lowest, and the parameters were close to those of Hep G2 cytosolic fractions. Real time RT-PCR using TaqMan probes demonstrated that the mRNA levels of SULT1A3 increased following BNF pretreatment, which paralleled the results from Western blotting showing the elevated levels of SULT1A3 proteins. These results suggest that the induction of SULT1A3 is mainly responsible for the elevated 4-OH-PL sulfation activities following the pretreatment of Hep G2 cells with BNF.
Junko Miyano; Shigeo Yamamoto; Nobumitsu Hanioka; Shizuo Narimatsu; Tsutomu Ishikawa; Kenichiro Ogura; Tadashi Watabe; Masuhiro Nishimura; Nobuhiko Ueda; Shinsaku Naito
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  69     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-03-07     Completed Date:  2005-04-12     Revised Date:  2013-01-25    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  941-50     Citation Subset:  IM    
Laboratory of Health Chemistry, Faculty of Pharmaceutical Sciences, Department of Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan.
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MeSH Terms
Cell Line
Dose-Response Relationship, Drug
Isoenzymes / biosynthesis,  genetics
Propranolol / analogs & derivatives*,  metabolism*
Sulfates / metabolism
Sulfotransferases / biosynthesis*,  genetics
beta-Naphthoflavone / pharmacology*
Reg. No./Substance:
0/Isoenzymes; 0/Sulfates; 10476-53-6/4-hydroxypropranolol; 525-66-6/Propranolol; 6051-87-2/beta-Naphthoflavone; EC 2.8.2.-/Sulfotransferases; EC phenol sulfotransferase

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