[Decrease of cyclin D1 and CDK4 protein and their related factors induced by quartz in human embryonic lung fibroblasts].
OBJECTIVE
To study the expression level of cyclin D1-CDK4 protein in human embryonic lung fibroblasts (HELF) induced by quartz, and to study whether the expression level of cyclin D1-CDK4 protein mediated by mitogen activated protein kinase (MAPK)/(AP-1) signaling pathways.


METHODS
Cells were harvested after stimulation 2 h for the detection of cytokines. Cyclin D1 and CDK4 (cyclin dependent kinase 4) proteins was measured by immunocytochemistry (IC) and Western blot (WB).


RESULTS
The exposure of HELF to crystalline quartz for 2 hours could cause the decrease of cyclin D1 and cyclin dependent kinase 4 (CDK4) protein expression level, (7.91 +/- 0.29) x 10(3) and (5.17 +/- 0.28) x 10(4) respectively, which was lower than that of the HELF group (P < 0.05). AG126 (chemical inhibitor of the extracellular signal regulated protein kinase (ERK) signaling pathway) and the dominant negative mutant of ERK2 (molecular inhibitor of ERK2), prevented the decrease of cyclin D1 and CDK4 protein expression level. The chemical inhibitor of c-Jun NH2-terminal amino kinase (JNK), SP600125, could prevent both cyclin D1 and CDK4 protein expression level decrease. But SB203580, the chemical inhibitor of p38, prevented neither cyclin D1 nor CDK4 protein expression level decrease. Curcumin could prevent CDK4 protein expression level decrease but not cyclin D1 protein.


CONCLUSIONS
ERKs and JNKs, but not p38, are responsible for the decrease of cyclin D1 and CDK4 protein expression level in HELF induced by quartz. AP-1 is responsible for the decrease of CDK4 expression level but not that of cyclin D1.
Shen
Fu-Hai
FH
National Institute of Occupation Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China.
Fan
Xue-Yun
XY
Liu
Bing-Ci
BC
D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism*; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000196:embryology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011791:Quartz / Q000633:toxicity*; D018808:Transcription Factor AP-1 / Q000378:metabolism
C530104:CCND1 protein, human; D018808:Transcription Factor AP-1; D019938:Cyclin D1; D011791:Quartz; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D020928:Mitogen-Activated Protein Kinases