title: Comparative and chemical proteomic approaches reveal gatifloxacin deregulates enzymes involved in glucose metabolism.
abstract: Gatifloxacin has been associated with increased risks of hypoglycemic and hyperglycemic side effects. In order to understand the molecular mechanism of gatifloxacin induced deregulation of glucose metabolism, a combination of comparative and chemical proteomic approaches were employed using yeast as a model system. Differential protein expression studies using two dimensional electrophoresis and mass spectrometry reveal that gatifloxacin deregulates the expression of key enzymes involved in glucose metabolism. Furthermore, affinity chromatography and LC-MS(E) analysis led to identification of enolase, as one of the key gatifloxacin binding proteins. Fluorescence spectrometric studies confirmed that the gatifloxacin indeed binds to enolase. Role of enolase in regulation of gatifloxacin induced dysglycemic effect is discussed.
authors: Proteomics Facility, Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune, India.
authors: Kesavan K
authors: KK
authors: Suresh
authors: Santosh D
authors: SD
authors: Bhosale
authors: Hirekodathakallu V
authors: HV
authors: Thulasiram
authors: Mahesh J
authors: MJ
authors: Kulkarni
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D002846:Chromatography, Affinity; D002853:Chromatography, Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D024841:Fluoroquinolones / Q000494:pharmacology*; D000077734:Gatifloxacin; D005947:Glucose / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D029701:Saccharomyces cerevisiae Proteins; D010751:Phosphopyruvate Hydratase; D005947:Glucose; D000077734:Gatifloxacin