P38 mitogen-activated protein kinase pathways are involved in the hypertrophy and apoptosis of cardiomyocytes induced by Porphyromonas gingivalis conditioned medium.
The surrounding medium of periodontal pathogen Porphyromonas gingivalis (P. gingivalis) increased cardiomyocyte hypertrophy and apoptosis whereas Actinobaeillus actinomycetemcomitans and Prevotella intermedia had no effects. The purpose of this study is to clarify the role of p38 pathway in P. gingivalis conditioned medium-induced H9c2 myocardial cell hypertrophy and apoptosis. DNA fragmentation, cellular morphology, nuclear condensation, p38 protein products, and mitochondrial-dependent apoptotic related proteins in cultured H9c2 myocardial cell were measured by agarose gel electrophoresis, immunofluorescence, DAPI, and western blotting following P. gingivalis conditioned medium and/or pre-administration of SB203580 (p38 inhibitor). The p38 protein products and associated activities in H9c2 cells were both upregulated by P. gingivalis conditioned medium. P. gingivalis conditioned medium increased cellular sizes, DNA fragmentation, nuclear condensation, mitochondrial Bcl2-associated death promoter (Bad), cytosolic cytochrome c (cyt c), and the activated form of caspase-9 proteins in H9c2 cells. The increased cellular sizes, DNA fragmentation, nuclear condensation, Bad, cyt c, and caspase-9 activities of H9c2 cells treated with P. gingivalis conditioned medium were all significantly reduced after pre-administration of SB203580. Our findings suggest that the activity of p38 signal pathway may be initiated by P. gingivalis conditioned medium and further activate mitochondrial-dependent apoptotic pathways leading to cell death in cultured H9c2 myocardial cells.
Wu
Hsi-Chin
HC
School of medicine, China Medical University and Hospital, Taichung, Taiwan.
Yeh
Yu-Lan
YL
Kuo
Wei-Wen
WW
Huang
Shu-Kuei
SK
Kuo
Wu-Hsien
WH
Hsieh
Dennis Jine-Yuan
DJ
Wu
Ching-Lin
CL
Tsai
Chang-Hai
CH
Lee
Shin-Da
SD
Huang
Chih-Yang
CY
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053453:Caspase 9 / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D045304:Cytochromes c / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D006984:Hypertrophy / Q000139:chemically induced / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000737:chemistry; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D016966:Porphyromonas gingivalis / Q000737:chemistry*; D011725:Pyridines / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D051025:bcl-Associated Death Protein / Q000187:drug effects / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*
C494819:BAD protein, human; D017077:Culture Media, Conditioned; D007093:Imidazoles; D007211:Indoles; D011725:Pyridines; D051025:bcl-Associated Death Protein; C007293:DAPI; D045304:Cytochromes c; D048051:p38 Mitogen-Activated Protein Kinases; D053453:Caspase 9; C093642:SB 203580