Abstract
Problem statement: Sulfotransferases (SULTs) are important phase II drug metabolizing enzymes. They also regulate the biological activities of various hormones. To the best of our knowledge, psychostimulants regulation of SULTs is basically not studied except one article reported that Methamphetamine (METH) treatment induced rat amygdale rSULT1A1 mRNA 4.3 fold by using microarray method to identify a series of candidate genes after single-dose METH treatment. The psychostimulant METH is used to treat disorders such as attention deficit, narcolepsy and obesity. It is also a highly addictive drug that causes serious social problems. The abuse of this drug leads to the damage of monoaminergic systems in the mammalian brain. It is important to understand how SULT expressions are regulated by psychostimulants. Approach: This study was performed to evaluate the effect of METH on SULT gene expressions in rat liver and brain. METH (0, 1, 5, 20 mg kg-1 day-1) was used to treat male and female rats for 7 days by oral administration. Rat livers and brains were collected 24 h after the final drug treatment. Western blot and real-time RT-PCR were used to investigate the effect of METH on SULT protein and mRNA expression, respectively, in rat liver and brain. Results: Proteins and mRNAs of rSULT1A1, rSULT2A1 and rSULT1E1 were induced in liver and brain of both male and female rats following METH treatment. rSULT1E1 was induced at much higher level compared to that of rSULT1A1 and rSULT2A1. Brain inductions were found to be much higher than those found in liver. Conclusion: These data suggest an important role of the central dopaminergic system in the regulation of liver and brain rSULT expressions.
Highlights
Sulfotransferases (SULTs) are one of the major superfamily of phase II drug metabolizing enzymes (Bojarova and Williams, 2008; Chapman et al, 2004; Gamage et al, 2006; Hempel et al, 2007; Kauffman, 2004; Rath et al, 2004; Runge-Morris and Kocarek, 2005; Wang and James, 2006)
We investigated the regulation of rSULT1A1, rSULT2A1 and rSULT1E1 by METH in both rat liver and rat brain
ATCCGTGCCTGGCTGTCTAT-3’, rSULT2A1-R642: METH regulation of rSULT1A1, rSULT2A1 and rSULT1E1 in rat liver: In female liver, Western blot data showed that rat SULT1A1 protein expression increased by about 44, 35 and 47%, respectively, after 1, 5, 20 mg kg−1 day−1 METH treatment for 7 days (Fig. 1A)
Summary
Sulfotransferases (SULTs) are one of the major superfamily of phase II drug metabolizing enzymes (Bojarova and Williams, 2008; Chapman et al, 2004; Gamage et al, 2006; Hempel et al, 2007; Kauffman, 2004; Rath et al, 2004; Runge-Morris and Kocarek, 2005; Wang and James, 2006). They catalyze the sulfation of hydroxyl-containing compounds. There are numerous important exceptions wherein the formation of chemically reactive sulfuric esters is an essential step in the metabolic pathways leading to carcinogenic responses (Hempel et al, 2007; Gallucci and Mickle, 2006)
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