Sangita Maiti Dutta*, Guangping Chen and Smarajit Maiti Pages 1 - 13 ( 13 )
Aims: To study the effects of blood glucose regulating compounds on human and rat sulfotransferases (SULTs) expressions.
Background: Phase-II enzymes, sulfotransferases catalyze the sulfuryl-group-transfer to endogenous/exogenous compounds. The alteration of expressions of SULTs may have influence on the sulfation rate of their corresponding substrates.
Objectives: The influence of the altered biotransformation property might impair or adjust several biochemical events, drug-drug interactions or modifications of bioaccumulation or excretion pattern of certain drug.
Methods: In this brief study, diabetes inducing drug streptozotocin (STZ 10 or 50 mg/kg to male Sprague Dawley rat for 2 weeks) or hyperglycemia controlling drug tolbutamide (TLB 0.1 or 10µM to human hepato-carcinoma cells, HepG2 for 10 days) was applied and the SULTs expressions were verified. Extensive protein-protein (STa, SULT2A1/DHEAST) interactions were studied by the STRING (Search-Tool-for-the-Retrieval-of-Interacting Genes/Proteins) Bioinformaticssoftware.
Results: Present result suggests that while STZ increased the STa (in rat) (dehydroepiandrosterone catalyzing SULT; DHEAST in human HepG2), tolbutamide decreased PPST (phenol catalyzing SULT) and DHEAST activity in human Hep G2 cells. Moderate decrease in MPST (monoamine catalyzing SULT) and EST (estrogen catalyzing) activity is noticed in this case also. STa/DHEAST was found to be highly interactive to SHBG/sex-hormone-binding-globulin; PPARα/lipidmetabolism-regulator; FABP1/fatty-acid-binding-protein.
Conclusions: In brief, streptozotocin and tolbutamide, two glycaemia-modifying drugs demonstrate rat and human SULTs regulating activities. The reciprocal nature of these two drugs on SULTs expression may be associated with their contrasting abilities in glucose-homeostasis. Possible association of some SULT-isoform with hepatic fat-regulations may indicate an unfocused link between calorie-metabolism and the glycemic-state of the individuals. Explorations of this work may uncover the role of sulfation metabolism of any biomolecule on cellular glycemic regulation.
Diabetes, streptozotocin, tolbutamide, sulfotransferase, rat liver, Hep G2
Department of Biological Sciences, Midnapore City College, Midnapore, West Bengal, Department of Physiological Sciences, Oklahoma State University, 264 McElroy Hall, Stillwater, OK 74078, Cell and Molecular Therapeutics Laboratory, Department of Biochemistry and Biotechnology, Oriental Institute of Science and Technology, Midnapore-721102, West Bengal