title: Taxol, a microtubule stabilizer, improves cardiac functional recovery during postischemic reperfusion in rat in vitro.
abstract: OBJECTIVE
  Microtubule disruption contributes to cellular and organic dysfunction, and is implicated in ischemia/reperfusion (I/R) injury. The purpose of this study was to explore the effects of taxol, a microtubule stabilizer, on cardiac functional recovery during reperfusion.
  
  
  METHODS
  Left ventricular developed pressure, left ventricular end-diastolic pressure, maximal time derivatives of pressure and the severity of ventricular arrhythmias were analyzed in isolated rat heart. Microtubule structure was immunohistochemically measured. Apoptosis and necrosis was identified with TUNEL or TTC staining, respectively. Mitochondrial permeability transition pore (mPTP) mRNA expression was examined by real-time polymerase chain reactions. mPTP opening, reactive oxygen species (ROS), and oxidative enzyme activities were measured with fluorometric or spectrophotometric techniques. Intracellular calcium concentration ([Ca(2+) ](i) ) and Ca(2+) transients were examined by Fura-2-AM and Fluo-3-AM, respectively. Cytosolic cytochrome c, sarcoplasmic reticulum Ca(2+) -ATPase (SERCA2), ryanodine receptors (RyR), phospholamban (PLB), and PLB phosphorylation were analyzed by Western blot. Effective refractory period (ERP) and afterpotential-mediated activity were detected using microelectrode.
  
  
  RESULTS
  Taxol improved the functional recovery of post-I/R. Taxol preserved the intact microtubule structure in reperfusion. mPTP mRNA expression was unchanged while the mPTP opening was reduced by taxol, and this effect was accompanied by the decreased ROS level caused by oxidative enzymes activities' changes. Taxol reduced apoptosis and the level of cytosolic cytochrome c in reperfusion. Taxol also promoted rapid recovery of [Ca(2+) ](i) , prevented reduction of the amplitude of Ca(2+) transients and shortened the decay time of Ca(2+) transients. The protein expression of SERCA2, RyR, and PLB remained unchanged in reperfusion. Taxol prevented the increase of Phospho-Thr17-PLB and Phospho-Ser16-PLB in reperfusion. In addition, taxol facilitated rapid recovery of ERP and counter-acted afterpotential-mediated activity.
  
  
  CONCLUSIONS
  Taxol may effectively improve cardiac functional recovery during reperfusion via inhibiting mPTP opening, ameliorating abnormal calcium homeostasis, and reducing the substrates associated with arrhythmias.
authors.affiliation: Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Xiao
authors.forename: Dandan
authors.initials: D
authors.lastname: Liang
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Luying
authors.initials: L
authors.lastname: Peng
authors.forename: Zhaonian
authors.initials: Z
authors.lastname: Zhou
authors.forename: Yi-Han
authors.initials: YH
authors.lastname: Chen
mesh_terms: D000200:Action Potentials; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control; D020013:Calcium Signaling / Q000187:drug effects; D002135:Calcium-Binding Proteins / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D009200:Myocardial Contraction / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009336:Necrosis; D018384:Oxidative Stress / Q000187:drug effects; D017239:Paclitaxel / Q000494:pharmacology*; D010477:Perfusion; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D020127:Recovery of Function; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D013997:Time Factors; D050257:Tubulin Modulators / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D045304:Cytochromes c; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017239:Paclitaxel; D017382:Reactive Oxygen Species; D019837:Ryanodine Receptor Calcium Release Channel; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D050257:Tubulin Modulators; D000099211:Phospholamban; C506948:Atp2a2 protein, rat