Title:Profiles of Two Glycaemia Modifying Drugs on the Expression of Rat and Human Sulfotransferases
Volume: 22
Issue: 3
Author(s): Sangita M. Dutta*, Guangping Chen and Smarajit Maiti
Affiliation:
- Department of Biological Sciences, Midnapore City College, Midnapore, West Bengal,India
Keywords:
Diabetes, streptozotocin, tolbutamide, sulfotransferase, rat liver, HepG2.
Abstract:
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 of its substrate
and other biomolecules.
Objectives: The influence of the altered biotransformation might alter different biochemical events, drug-drug
interactions and 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) Bioinformatics-software.
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 HepG2 cells. Moderate decreases of MPST (monoamine catalyzing SULT) and EST (estrogen
catalyzing) activities are noticed in this case. STa/DHEAST was found to be highly interactive to SHBG/-
sex-hormone-binding-globulin; PPARα/lipid-metabolism-regulator; FABP1/fatty-acid-binding-protein.
Conclusion: Streptozotocin and tolbutamide, these two glycaemia-modifying drugs demonstrated regulation of
rat and human SULTs activities. The reciprocal nature of these two drugs on SULTs expression may be associated
with their contrasting abilities in influencing glucose-homeostasis. Possible association of certain SULT-isoform
with hepatic fat-regulations may indicate an unfocused link between calorie-metabolism and the
glycemic-state of an individual. Explorations of this work may uncover the role of sulfation metabolism of specific
biomolecule on cellular glycemic regulation.