首页 | 本学科首页   官方微博 | 高级检索  
     


Transport Alteration of 4-Phenyl Butyric Acid Mediated by a Sodium- and Proton-Coupled Monocarboxylic Acid Transporter System in ALS Model Cell Lines (NSC-34) Under Inflammatory States
Authors:Asmita Gyawali  Young-Sook Kang
Affiliation:College of Pharmacy and Drug Information Research Institute, Sookmyung Women''s University, Seoul, Republic of Korea
Abstract:4-Phenyl butyric acid (PBA) has histone deacetylase inhibitory and neuroprotective effects. We aimed to examine the transport alteration activity of PBA in control (WT) and disease (MT) model cell lines of an amyotrophic lateral sclerosis (ALS) model. The transport characteristics of PBA were examined uptake rates and mRNA expression levels in NSC-34 cell lines. PBA uptake was pH, sodium, and concentration dependent. The Km and Vmax values for PBA uptake in the MT were more than two-fold higher than those in the WT. The presence of monocarboxylic acids (MA) and inhibitors of MA transporter (MCT) inhibited the uptake of PBA. PBA showed competitive inhibition in the presence of MAs in both cell lines. SiRNA transfection studies showed that PBA can be transported to NSC-34 cell lines through sodium-coupled MCT1. TNF-α and H2O2 increased, but LPS and glutamate reduced the uptake rate after the pretreatment of the MT cell lines. SMCT1 mRNA expression levels, in the presence of oxidative stress inducing agents, showed consistent results with the uptake results. These results demonstrate that PBA can be transported to the ALS model NSC-34 cell lines by sodium- and proton-coupled MCTs, and MA plays a vital role in the prevention of neurodegenerative diseases.
Keywords:4-Phenyl butyric acid  PBA  NSC-34 cell lines  Amyotrophic lateral sclerosis  ALS  Monocarboxylic acids  MA  Monocarboxylic acid transporter  MCT  Neurodegenerative disease  ND  AA"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0070"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Acetic acid  ALS"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0080"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Amyotrophic lateral sclerosis  CHC"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0090"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Alpha-cyano-4-hydroxycinnamate  ECF"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0100"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Extracellular fluid  ER"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0110"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Endoplasmic reticulum  FCCP"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0120"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Carbonyl cyanide trifluoromethoxyphenylhydrazone  HDAC"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0130"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Histone deacetylase  hydrogen peroxide  Non-saturable uptake clearance  Inhibition constant  Michaelis-Menten constant  LA"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0180"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Lactic acid  MA"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0190"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Monocarboxylic acid  MCT"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0200"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Monocarboxylic acid transporter  MND"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0210"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Motor neuron disease  MN"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0220"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Motor neuron  MT"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0230"  },"  $$"  :[{"  #name"  :"  text"  ,"  $$"  :[{"  #name"  :"  __text__"  ,"  _"  :"  Mutant type (NSC-34/hSOD1"  },{"  #name"  :"  sup"  ,"  $"  :{"  loc"  :"  post"  },"  _"  :"  G93A"  },{"  #name"  :"  __text__"  ,"  _"  :"  )  ND"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0240"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Neurodegenerative  NMDG"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0250"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  N-methyl glucosamine  PBA"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0260"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  4-phenylbutyric acid  ROS"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0270"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Reactive oxygen species  SA"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0280"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Salicylic acid  SPB"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0290"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Sodium phenyl butyrate  SMCT1"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0300"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Sodium-dependent monocarboxylate transporter  TNF-α"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0310"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Tumor necrosis factor- alpha  Maximum transport velocity  VPA"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0330"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Valproic acid  WT"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0340"  },"  $$"  :[{"  #name"  :"  text"  ,"  $$"  :[{"  #name"  :"  __text__"  ,"  _"  :"  Wild type (NSC-34/hSOD1"  },{"  #name"  :"  sup"  ,"  $"  :{"  loc"  :"  post"  },"  _"  :"  wt"  },{"  #name"  :"  __text__"  ,"  _"  :"  )
本文献已被 ScienceDirect 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号