Toxicity of TDCPP and TCEP on PC12 cell: changes in CAMKII, GAP43, tubulin and NF-H gene and protein levels.
TDCPP and TCEP are two major types of organophosphorus flame retardants (OPFRs) that are bioaccumulative and persistent in the environment. The toxicity effects of TDCPP and TCEP on PC12 cell are not well understood. In the present study, we investigated morphology, viability and apoptosis in cultured PC12 cells in response to TDCPP and TCEP. The mRNA and protein expression levels of CAMKII, GAP43, tubulin and NF-H were quantified in PC12 cells treated with varying concentrations of the two agents. Results indicate that, upon treatment with the two OPFRs, cell growth decreased, apoptosis increased, morphology was altered and significant changes were found in the gene and protein levels. Treatment with TDCPP caused a reduction in the levels of each of the six proteins studied and in the gene levels of GAP43, NF-H and the two tubulins, but it resulted in an increase in CAMKII gene levels. Treatment with TCEP resulted in similar changes in gene levels to TDCPP and led to decreases in the protein levels of GAP43 and the tubulins while increasing the CAMKII and NF-H protein levels. These results suggest that changes in the gene and protein levels of the regulatory proteins (CAMKII, GAP43) and the structural proteins (tubulin, NF-H) are due to different mechanisms of the toxins, and these proteins may be useful biomarkers for the cytotoxicity and neurotoxicity.
Tianjin Institute of Hygienic and Environmental Medicinal Science, A Key Laboratory of Risk Assessment and Control for Environment and Food Safety, Tianjin 300050, China.
Na
N
Ta
Tianjin Institute of Hygienic and Environmental Medicinal Science, A Key Laboratory of Risk Assessment and Control for Environment and Food Safety, Tianjin 300050, China.
Chaonan
C
Li
Tianjin Institute of Hygienic and Environmental Medicinal Science, A Key Laboratory of Risk Assessment and Control for Environment and Food Safety, Tianjin 300050, China. Electronic address: yanjunfang1973@163.com.
Yanjun
Y
Fang
Tianjin Institute of Hygienic and Environmental Medicinal Science, A Key Laboratory of Risk Assessment and Control for Environment and Food Safety, Tianjin 300050, China.
Huanliang
H
Liu
Tianjin Institute of Hygienic and Environmental Medicinal Science, A Key Laboratory of Risk Assessment and Control for Environment and Food Safety, Tianjin 300050, China.
Bencheng
B
Lin
Tianjin Institute of Hygienic and Environmental Medicinal Science, A Key Laboratory of Risk Assessment and Control for Environment and Food Safety, Tianjin 300050, China.
Hong
H
Jin
Tianjin Institute of Hygienic and Environmental Medicinal Science, A Key Laboratory of Risk Assessment and Control for Environment and Food Safety, Tianjin 300050, China.
Lei
L
Tian
Tianjin Institute of Hygienic and Environmental Medicinal Science, A Key Laboratory of Risk Assessment and Control for Environment and Food Safety, Tianjin 300050, China.
Huashan
H
Zhang
Tianjin Institute of Hygienic and Environmental Medicinal Science, A Key Laboratory of Risk Assessment and Control for Environment and Food Safety, Tianjin 300050, China.
Wei
W
Zhang
Tianjin Institute of Hygienic and Environmental Medicinal Science, A Key Laboratory of Risk Assessment and Control for Environment and Food Safety, Tianjin 300050, China. Electronic address: zhugexi2003@sina.com.
Zhuge
Z
Xi
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D017931:DNA Primers; D005411:Flame Retardants / Q000633:toxicity*; D005434:Flow Cytometry; D019922:GAP-43 Protein / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000378:metabolism* / Q000633:toxicity*; D016716:PC12 Cells; D010720:Phosphines / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D014404:Tubulin / Q000378:metabolism*
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017931:DNA Primers; D005411:Flame Retardants; D019922:GAP-43 Protein; D016900:Neurofilament Proteins; D009943:Organophosphorus Compounds; D010720:Phosphines; D012333:RNA, Messenger; D014404:Tubulin; C051774:neurofilament protein H; C080938:tris(2-carboxyethyl)phosphine; C016805:tris(1,3-dichloro-2-propyl)phosphate
Cytotoxicity; Gene; Neurotoxicity; PC12; Protein; TDCPP/TCEP