title: Isosteviol Sensitizes sarcKATP Channels towards Pinacidil and Potentiates Mitochondrial Uncoupling of Diazoxide in Guinea Pig Ventricular Myocytes.
abstract: KATP channel is an important mediator or factor in physiological and pathological metabolic pathway. Activation of KATP channel has been identified to be a critical step in the cardioprotective mechanism against IR injury. On the other hand, desensitization of the channel to its opener or the metabolic ligand ATP in pathological conditions, like cardiac hypertrophy, would decrease the adaption of myocardium to metabolic stress and is a disadvantage for drug therapy. Isosteviol, obtained by acid hydrolysis of stevioside, has been demonstrated to play a cardioprotective role against diseases of cardiovascular system, like anti-IR injury, antihypertension, antihyperglycemia, and so forth. The present study investigated the effect of isosteviol (STV) on sarcKATP channel current induced by pinacidil and mitochondrial flavoprotein oxidation induced by diazoxide. Our results showed that preincubating cells with STV not only increased the current amplitude and activating rate of sarcKATP channels induced by pinacidil but also potentiated diazoxide-elicited oxidation of flavoprotein in mitochondria.
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China; Pre-Incubator for Innovative Drugs and Medicine, South China University of Technology, Guangzhou 510006, China; Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, South China University of Technology, Guangzhou 510006, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Fan
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China; Pre-Incubator for Innovative Drugs and Medicine, South China University of Technology, Guangzhou 510006, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wen
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China; Pre-Incubator for Innovative Drugs and Medicine, South China University of Technology, Guangzhou 510006, China.
authors.forename: Yaoxu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China; Pre-Incubator for Innovative Drugs and Medicine, South China University of Technology, Guangzhou 510006, China.
authors.forename: Lijie
authors.initials: L
authors.lastname: Huang
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China; Pre-Incubator for Innovative Drugs and Medicine, South China University of Technology, Guangzhou 510006, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China; Pre-Incubator for Innovative Drugs and Medicine, South China University of Technology, Guangzhou 510006, China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Yin
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China; Pre-Incubator for Innovative Drugs and Medicine, South China University of Technology, Guangzhou 510006, China; Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, South China University of Technology, Guangzhou 510006, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D003981:Diazoxide / Q000494:pharmacology*; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D005420:Flavoproteins / Q000378:metabolism; D005453:Fluorescence; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology*; D015640:Ion Channel Gating / Q000187:drug effects; D054086:KATP Channels / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D020110:Pinacidil / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
chemical_list: D020746:Calcium Channels, L-Type; D045786:Diterpenes, Kaurane; D005420:Flavoproteins; D054086:KATP Channels; D017382:Reactive Oxygen Species; C515747:isosteviol; D020110:Pinacidil; D003981:Diazoxide; D005905:Glyburide; D000111:Acetylcysteine