p38 inhibitor intensified cell death in antimycin A-treated As4.1 juxtaglomerular cells via the enhancement of GSH depletion.
Antimycin A (AMA) inhibits succinate oxidase, NADH oxidase and mitochondrial electron transport chain between cytochrome b and c. Here, we investigated the effects of AMA and/or mitogen-activated protein kinase (MAPK) inhibitors on As4.1 juxtaglomerular cells in relation to cell growth, cell death, reactive oxygen species (ROS) and glutathione (GSH) levels. Treatment with 50 nM AMA inhibited the growth of As4.1 cells at 48 hours and induced apoptosis, which was accompanied by the loss of mitochondrial membrane potential (DeltaPsi(m)). AMA increased ROS levels including that of intracellular O(2)(*-). AMA also induced GSH depletion. MEK inhibitor did not affect cell growth, cell death, DeltaPsi(m) loss, ROS level or GSH depletion in AMA-treated As4.1 cells. c-Jun N-terminal kinase (JNK) inhibitor also did not influence cell growth, cell death, ROS level and GSH depletion but did slightly increase DeltaPsi(m) loss. Treatment with p38 inhibitor magnified cell growth inhibition by AMA and increased cell death, DeltaPsi(m) loss and GSH depletion in AMA-treated As4.1 cells. Conclusively, p38 inhibitor intensified cell death in AMA-treated As4.1 cells. The changes of GSH content rather than ROS level by AMA and/or MAPK inhibitors were more closely related to the growth and death of As4.1 cells.
Han
Yong Hwan
YH
Department of Physiology, Medical School, Chonbuk National University, JeonJu, Republic of Korea.
Moon
Hwa Jin
HJ
You
Bo Ra
BR
Kim
Sung Zoo
SZ
Kim
Suhn Hee
SH
Park
Woo Hyun
WH
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D005419:Flavonoids / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D007606:Juxtaglomerular Apparatus / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007680:Kidney Neoplasms; D051379:Mice; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D005419:Flavonoids; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D017382:Reactive Oxygen Species; D000968:Antimycin A; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005978:Glutathione; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one