title: Porphyromonas gingivalis-related cardiac cell apoptosis was majorly co-activated by p38 and extracellular signal-regulated kinase pathways.
abstract: OBJECTIVE
  Little is known about the pathogenesis of apoptosis caused in cardiac tissues by periodontitis pathogens. The purpose of this study was to determine the related effect of periodontal pathogen Porphyromonas gingivalis on cardiac cell apoptosis.
  
  
  METHODS
  DNA fragmentation, nuclear condensation and activated apoptotic caspases were measured by agarose gel electrophoresis, nuclear DAPI (4',6-diamidine-2-phenylindole dihydrochloride) stain and western blotting analysis following the surrounding medium of P. gingivalis and/or pre-administration of SB203580 (p38 inhibitor), U0126 [mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor], LY294002 [phosphoinositide 3-kinase (PI3K) inhibitor], cyclosporine A (CsA: calcineurin inhibitor), and Sp600125 [c-Jun N-terminal kinase (JNK) inhibitor] in cultured cardiac H9c2 cells.
  
  
  RESULTS
  The surrounding medium of periodontal pathogen P. gingivalis increased DNA fragmentation, nuclear condensation and the activated apoptotic caspase-3, -8, and -9 proteins in H9c2 cells. DNA fragmentation and nuclear condensation of H9c2 cells treated with P. gingivalis medium were completely blocked by SB203580 plus U0126 and were decreased after pre-administration of SB203580 only, U0126 only, LY294002, CsA, but were increased by Sp600125.
  
  
  CONCLUSIONS
  Our findings suggest that the development of cardiac cell apoptosis can be directly induced by P. gingivalis medium. Porphyromonas gingivalis-related H9c2 cell apoptosis was mainly co-activated by p38 and ERK pathways and may be involved in death receptor-dependent (caspase 8) and mitochondria (caspase 9)-dependent apoptotic pathways. Porphyromonas gingivalis-related cardiac cell apoptosis was also partially mediated by PI3K or calcineurin signaling pathways, whereas the JNK pathway might play a protective role in P. gingivalis-related cardiac cell apoptosis.
authors.affiliation: School of Physical Therapy, Chung-Shan Medical University, Taichung, Taiwan.
authors.forename: Shin-Da
authors.initials: SD
authors.lastname: Lee
authors.forename: Cheng-Chung
authors.initials: CC
authors.lastname: Wu
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Kuo
authors.forename: James A
authors.initials: JA
authors.lastname: Lin
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Hwang
authors.forename: Min-Chi
authors.initials: MC
authors.lastname: Lu
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Chen
authors.forename: His-Hsien
authors.initials: HH
authors.lastname: Hsu
authors.forename: Chin-Kun
authors.initials: CK
authors.lastname: Wang
authors.forename: Sheng-Huang
authors.initials: SH
authors.lastname: Chang
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D002070:Butadienes / Q000494:pharmacology; D065095:Calcineurin Inhibitors; D020169:Caspases / Q000502:physiology; D002467:Cell Nucleus / Q000648:ultrastructure; D002867:Chromones / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D053938:DNA Fragmentation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D009025:Morpholines / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology*; D009570:Nitriles / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D016966:Porphyromonas gingivalis / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D000873:Anthracenes; D002070:Butadienes; D065095:Calcineurin Inhibitors; D002867:Chromones; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D007093:Imidazoles; D007211:Indoles; D009025:Morpholines; D009570:Nitriles; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011725:Pyridines; C113580:U 0126; C432165:pyrazolanthrone; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C007293:DAPI; D016572:Cyclosporine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D020169:Caspases; C093642:SB 203580