JNK and p38 inhibitors increase and decrease apoptosis, respectively, in pyrogallol-treated calf pulmonary arterial endothelial cells.
Pyrogallol (PG) as a polyphenol compound induces apoptosis in several types of cells. Here, we investigated the effects of MAPK inhibitors on PG-treated calf pulmonary artery endothelial cells (CPAEC) in relation to cell death, ROS and GSH. PG inhibited the growth of CPAEC and also induced cell death, which was accompanied by the loss of mitochondrial membrane potential (MMP; DeltaPsi(m)). PG decreased the ROS level and increased the GSH depleted cell number in CPAEC. JNK inhibitor intensified the growth inhibition by PG whereas p38 inhibitor attenuated the growth inhibition. While MEK and p38 inhibitors decreased CPAEC death by PG, JNK inhibitor increased. None of the MAPK inhibitors significantly increased ROS level in PG-treated CPAEC. JNK inhibitor increased GSH depleted cell number in PG-treated CPAEC whereas p38 inhibitor decreased the number. MAPK inhibitors differently affected cell growth, death, ROS and GSH levels in control CPACE. In conclusion, PG induced apoptosis via the loss of MMP (DeltaPsi(m)) in CPAEC, which is accompanied by GSH depletion. JNK and p38 inhibitors increased and decreased apoptosis in PG-treated CPAEC, respectively, which were correlated with GSH depletion.
Han
Yong Hwan
YH
Department of Physiology, Medical School, Centers for Healthcare Technology Development Institute for Medical Sciences, Chonbuk National University, JeonJu 561-180, Korea.
Moon
Hwa Jin
HJ
You
Bo Ra
BR
Kim
Sung Zoo
SZ
Kim
Suhn Hee
SH
Park
Woo Hyun
WH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D005978:Glutathione / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000166:cytology; D011748:Pyrogallol / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
D047428:Protein Kinase Inhibitors; D011748:Pyrogallol; D013481:Superoxides; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005978:Glutathione