title: Palmitic acid-induced lipotoxicity and protection by (+)-catechin in rat cortical astrocytes.
abstract: BACKGROUND
  Astrocytes do not only maintain homeostasis of the extracellular milieu of the neurons, but also play an active role in modulating synaptic transmission. Palmitic acid (PA) is a saturated fatty acid which, when being excessive, is a significant risk factor for lipotoxicity. Activation of astrocytes by PA has been shown to cause neuronal inflammation and demyelination. However, direct damage by PA to astrocytes is relatively unexplored. The aim of this study was to identify the mechanism(s) of PA-induced cytotoxicity in rat cortical astrocytes and possible protection by (+)-catechin.
  
  
  METHODS
  Cytotoxicity and endoplasmic reticulum (ER) markers were assessed by MTT assay and Western blotting, respectively. Cytosolic Ca(2+) and mitochondrial membrane potential (MMP) were measured microfluorimetrically using fura-2 and rhodamine 123, respectively. Intracellular reactive oxygen species (ROS) production was assayed by the indicator 2'-7'-dichlorodihydrofluorescein diacetate.
  
  
  RESULTS
  Exposure of astrocytes to 100μM PA for 24h resulted in apoptotic cell death. Whilst PA-induced cell death appeared to be unrelated to ER stress and perturbation in cytosolic Ca(2+) signaling, it was likely a result of ROS production and subsequent MMP collapse, since ascorbic acid (anti-oxidant, 100μM) prevented PA-induced MMP collapse and cell death. Co-treatment of astrocytes with (+)-catechin (300μM), an anti-oxidant found abundantly in green tea, significantly prevented PA-induced ROS production, MMP collapse and cell death.
  
  
  CONCLUSIONS
  Our results suggest that PA-induced cytotoxicity in astrocytes may involve ROS generation and MMP collapse, which can be prevented by (+)-catechin.
authors.affiliation: Department of Anesthesiology, China Medical University and Hospital, Taichung, Taiwan; Department of Anesthesiology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong; Department of Anesthesiology, Shandong University Nanshan Branch of Qilu Hospital, China.
authors.forename: Kar-Lok
authors.initials: KL
authors.lastname: Wong
authors.affiliation: Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan.
authors.forename: Yu-Ru
authors.initials: YR
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, China Medical University and Hospital, Taichung, Taiwan.
authors.forename: Ka-Shun
authors.initials: KS
authors.lastname: Cheng
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Medical University Wan Fan Hospital, Taipei, Taiwan.
authors.forename: Paul
authors.initials: P
authors.lastname: Chan
authors.affiliation: Department of Anesthesiology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong.
authors.forename: Chi-Wai
authors.initials: CW
authors.lastname: Cheung
authors.affiliation: Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan.
authors.forename: Dah-Yuu
authors.initials: DY
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, China Medical University and Hospital, Taichung, Taiwan.
authors.forename: Tzu-Hui
authors.initials: TH
authors.lastname: Su
authors.affiliation: Department of Cardiovascular Surgery, Shanghai East Hospital, Tongji University, Shanghai, China. Electronic address: Zhongmin_liu@sina.com.cn.
authors.forename: Zhong-Min
authors.initials: ZM
authors.lastname: Liu
authors.affiliation: Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan. Electronic address: ymleung@mail.cmu.edu.tw.
authors.forename: Yuk-Man
authors.initials: YM
authors.lastname: Leung
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000187:drug effects* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002392:Catechin / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000166:cytology; D003600:Cytosol / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D019308:Palmitic Acid / Q000633:toxicity*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D019308:Palmitic Acid; D002392:Catechin; D002118:Calcium
keywords: (+)-Catechin; Astrocytes; Mitochondrial membrane potential; Palmitic acid; Reactive oxygen species