title: Anthocyanins protect against kainic acid-induced excitotoxicity and apoptosis via ROS-activated AMPK pathway in hippocampal neurons.
abstract: BACKGROUND
  Excitotoxicity is an important mechanism involved in neurodegeneration. Kainic acid (KA)-induced excitotoxicity results an unfavorable stress, and we investigated the signaling pathways activated in such conditions.
  
  
  OBJECTIVE
  Here, we sought to determine the cellular and biochemical benefits of anthocyanins extracted from Korean black bean against KA-induced excitotoxicity and neuronal cell death.
  
  
  RESULTS
  Mouse hippocampal cell line (HT22) and primary prenatal rat hippocampal neurons were treated with KA to induce excitotoxicity. Incubation of the cells with KA alone significantly decreased cell viability, elevated intracellular Ca(2+) level, increased generation of reactive oxygen species (ROS) and loss of mitochondrial membrane potential (Δψ(M)). These events were accompanied by sustained phosphorylation and activation of AMP-activated protein kinase (AMPK). Kainic acid induced upregulation of Bax, decrease in Bcl-2, release of cytochrome-c, and activation of caspase-3 in both cell types. Anthocyanins attenuated KA-induced dysregulation of Ca(2+), ROS accumulation, activation of AMPK, and increase in percentage of apoptotic cells. Pretreatment of the cells with compound C, an inhibitor of AMPK, diminished the KA-induced activation of AMPK and caspase-3. The activation of AMPK through elevation of cellular ROS and Ca(2+) levels is required for KA-induced apoptosis in hippocampal neurons.
  
  
  CONCLUSIONS
  In summary, our data suggest that although anthocyanins have diverse activities, at least part of their beneficial effects against KA-induced hippocampal degeneration can be attributed to their well-recognized antioxidant properties.
authors.affiliation: Department of Biology, College of Natural Sciences (RINS), Applied Life Science (BK 21) Gyeongsang National University, Jinju, Korea.
authors.forename: Ikram
authors.initials: I
authors.lastname: Ullah
authors.forename: Hyun Young
authors.initials: HY
authors.lastname: Park
authors.forename: Myeong Ok
authors.initials: MO
authors.lastname: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007608:Kainic Acid / Q000633:toxicity*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000872:Anthocyanins; D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D055372:AMP-Activated Protein Kinases; D007608:Kainic Acid; D002118:Calcium
keywords: Anthocyanins; Excitotoxicity; Kainic acid; Neurodegeneration; Neuroprotection