Porphyromonas gingivalis-related cardiac cell apoptosis was majorly co-activated by p38 and extracellular signal-regulated kinase pathways.
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.
Lee
Shin-Da
SD
School of Physical Therapy, Chung-Shan Medical University, Taichung, Taiwan.
Wu
Cheng-Chung
CC
Kuo
Wei-Wen
WW
Lin
James A
JA
Hwang
Jin-Ming
JM
Lu
Min-Chi
MC
Chen
Li-Ming
LM
Hsu
His-Hsien
HH
Wang
Chin-Kun
CK
Chang
Sheng-Huang
SH
Huang
Chih-Yang
CY
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
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