Mechanism of silica-induced ROS generation in Rat2 fibroblast cells.
Reactive oxygen species (ROS) play an important role in cell signaling pathway. Previously, we found that silica induced immediate ROS generation and sequential cellular responses such as kinase activation in Rat2 cells as well as an increase of intracellular calcium concentration in A549 cells. However, the detailed mechanism underlying the immediate ROS generation induced by silica in fibroblast cells remains to be elucidated. Therefore, in the present study, we investigated the mechanism of ROS generation by silica within Rat2 fibroblast cells by examining the effects of a diverse group of inhibitors for the enzymes related with signal transduction events. Inhibitors for protein tyrosine kinase (PTK), phospholipase C (PLC), protein kinase C (PKC) and calmodulin (CaM) kinase II effectively suppressed ROS generation in silica-stimulated Rat2 cells, whereas those for protein kinase A and phospholipase A(2) did not. Diphenyleneiodonium chloride (DPI), an inhibitor for NADPH oxidase was also found to be effective in inhibiting silica-induced ROS generation. These results suggest that PTK, PLC, PKC, CaM kinase II, and NADPH oxidase are all involved in signal transduction pathways for ROS generation in silica-stimulated Rat2 cells.
Kim
Kyoung-Ah
KA
Department of Occupational and Environmental Medicine, St. Mary's Hospital, The Catholic University of Korea, 62 Youido-dong, Youngdungpo-gu, Seoul 150-010, South Korea.
Kim
Young-Hoon
YH
Seok Seo
Min
M
Kyu Lee
Woon
W
Won Kim
Seung
S
Kim
Hongtae
H
Lee
Kweon-Haeng
KH
Shin
In-Chul
IC
Han
Joong-Soo
JS
Joong Kim
Hyoung
H
Lim
Young
Y
D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D019833:Genistein / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D012822:Silicon Dioxide / Q000494:pharmacology* / Q000633:toxicity; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D012822:Silicon Dioxide; D019833:Genistein; D011494:Protein Kinases; D010738:Type C Phospholipases; D011796:Quinacrine