Methamphetamine regulation of sulfotransferase 1A1 and 2A1 expression in rat brain sections

Abstract

Sulfotransferase catalyzed sulfation regulates the biological activities of various neurotransmitters/hormones and detoxifies xenobiotics. Rat sulfotransferase rSULT1A1 catalyzes the sulfation of neurotransmitters and xenobiotic phenolic compounds. rSULT2A1 catalyzes the sulfation of hydroxysteroids and xenobiotic alcoholic compounds. In this work, Western blot and real-time RT-PCR were used to investigate the effect of methamphetamine on rSULT1A1 and rSULT2A1 protein and mRNA expression in rat cerebellum, frontal cortex, hippocampus, and striatum. After 1-day treatment, significant induction of rSULT1A1 was observed only in the cerebellum; rSULT2A1 was induced significantly in the cerebellum, frontal cortex, and hippocampus. After 7-days of exposure, rSULT1A1 was induced in the cerebellum, frontal cortex, and hippocampus, while rSULT2A1 was induced significantly in all four regions. Western blot results agreed with the real-time RT-PCR results, suggesting that the induction occurred at the gene transcriptional level. Results indicate that rSULT1A1 and rSULT2A1 are expressed in rat frontal cortex, cerebellum, striatum, and hippocampus. rSULT1A1 and rSULT2A1are inducible by methamphetamine in rat brain sections in a time dependable manner. rSULT2A1 is more inducible than rSULT1A1 by methamphetamine in rat brain sections. Induction activity of methamphetamine is in the order of cerebellum > frontal cortex, hippocampus > striatum. These results suggest that the physiological functions of rSULT1A1 and rSULT2A1 in different brain regions can be affected by methamphetamine.

Exogenous dopamine induces dehydroepiandrosterone sulfotransferase (rSULT2A1) in rat liver and changes the pharmacokinetic profile of moxifloxacin in rats

“…One recent paper demonstrated that SULT1A3 could be induced by DA in vitro, indicating the role of SULT1A3 in CNS by protecting neuronal cells from DA toxicity [25]. Besides, our previous results showed that methamphetamine, a structural analogue of DA, could induce the expressions of rSULT2A1 remarkably in rat liver and brain [23,24]. Our recent data in vitro also revealed that the activity of SULT2A1 in HepG2 cells increased significantly after the treatment with DA, and the expression of SULT2A1 was significantly induced by specific D1 agonists (SKF-38393 and SKF 82958) that activating D1 signaling pathway selectively [26].…”

“…Protein level of rSULT2A1 in male and female rat liver cytosol was investigated by western blot analysis [23]. In brief, 50 mg of protein from rat liver were separated in a 12% polyacrylamide gel by an electrophoresis system (Bio-Rad, Hercules, CA, USA).…”

Intratumoral estrogen sulfotransferase induction contributes to the anti-breast cancer effects of the dithiocarbamate derivative TM208

“…In vivo, tumor-bearing mice were treated with TM208 for 18 d, and cytosol samples from the tumors were prepared as previously described [36] .…”

“…Western blot analysis was conducted as described in a previous study [36] . Total protein (50 μg) was separated by SDS-12% w/v polyacrylamide gel electrophoresis and transferred to PVDF membranes (Pierce, Rockford, IL, USA).…”

“…Radioactive assay on the activity of EST Tumor-bearing mice were treated with TM208 for 18 d, and the cytosol of the tumors was prepared as previously described [36] . The reaction mixture, containing 0.15 μmol/L 3 H-estradiol as the substrate [38] , 50 mmol/L Tris buffer (pH 6.2), 20 μmol/L PAPS, and 20 μL of cytosol, as well as 100 μg of total protein as the enzyme source, in a total volume of 250 μL, was incubated at 37.0 °C for 30 min.…”