title: Luteolin Enhances Sarcoplasmic Reticulum Ca2+-ATPase Activity through p38 MAPK Signaling thus Improving Rat Cardiac Function after Ischemia/Reperfusion.
abstract: OBJECTIVE
  A major challenge for current therapeutic strategies against ischemia/reperfusion (I/R) is the lack of effective drugs. Considering luteolin enhances the activity of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) to improve the systolic/diastolic function of rat hearts and cardiomyocytes during the I/R process, we studied the regulatory function of the p38 MAPK pathway in this protective mechanism.
  
  
  METHODS
  Isolated cardiomyocytes and perfused hearts were separately divided into five groups and used to investigate I/R. The phosphorylation of p38 and phospholamban (p-PLB), the levels and activity of SERCA2a and the levels of proteins related to apoptosis were measured. Apoptotic cells were assessed using the TUNEL assay. Single-cell shortening, Ca2+ transients, and the decay of the mitochondrial membrane potential (Δψm) were detected.
  
  
  RESULTS
  The p38 MAPK pathway was activated during the I/R process, and inhibiting it with SB203580 promoted p-PLB, which enhanced the activity of SERCA2a and relieved the calcium overload to promote the recovery of the Δψm and reduce cardiomyocyte apoptosis in I/R. Luteolin also suppressed the activation of the p38 MAPK pathway and showed cardioprotective effects during I/R injury.
  
  
  CONCLUSIONS
  We conclude that luteolin enhances SERCA2a activity to improve systolic/diastolic function during I/R in rat hearts and cardiomyocytes by attenuating the inhibitive effects of the p38 pathway on p-PLB.
authors.forename: Shasha
authors.initials: S
authors.lastname: Zhu
authors.forename: Tongda
authors.initials: T
authors.lastname: Xu
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Luo
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Haochen
authors.initials: H
authors.lastname: Xuan
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Ma
authors.forename: Defeng
authors.initials: D
authors.lastname: Pan
authors.forename: Dongye
authors.initials: D
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D005786:Gene Expression Regulation; D007093:Imidazoles / Q000494:pharmacology; D047311:Luteolin / Q000494:pharmacology*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009924:Organ Culture Techniques; D010766:Phosphorylation; D061251:Primary Cell Culture; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D002316:Cardiotonic Agents; D007093:Imidazoles; D047311:Luteolin; D011725:Pyridines; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D048051:p38 Mitogen-Activated Protein Kinases; D000099211:Phospholamban; C093642:SB 203580
keywords: Ischemia/reperfusion; Luteolin; SERCA2a; Systolic/diastolic function; p38 MAPK pathway