Full Text:   <1704>

CLC number: R995

On-line Access: 

Received: 2006-12-29

Revision Accepted: 2007-03-16

Crosschecked: 0000-00-00

Cited: 4

Clicked: 4112

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
1. Reference List
Open peer comments

Journal of Zhejiang University SCIENCE B 2007 Vol.8 No.6 P.422~427


Effect of lead on ERK activity and the protective function of bFGF in rat primary culture astroglia

Author(s):  ZHANG Ying, YE Li-ping, WANG Biao, CAO Shi-cheng, SUN Li-guang

Affiliation(s):  Department of Biochemistry and Molecule Biology, College of Basic Medical Sciences, China Medical University, Shenyang 110001, China

Corresponding email(s):   ydslg@163.com

Key Words:  Lead, Astroglia, Extracellular signal regulated kinase (ERK), Basic fibroblast growth factor (bFGF)

ZHANG Ying, YE Li-ping, WANG Biao, CAO Shi-cheng, SUN Li-guang. Effect of lead on ERK activity and the protective function of bFGF in rat primary culture astroglia[J]. Journal of Zhejiang University Science B, 2007, 8(6): 422~427.

@article{title="Effect of lead on ERK activity and the protective function of bFGF in rat primary culture astroglia",
author="ZHANG Ying, YE Li-ping, WANG Biao, CAO Shi-cheng, SUN Li-guang",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Effect of lead on ERK activity and the protective function of bFGF in rat primary culture astroglia
%A YE Li-ping
%A WANG Biao
%A CAO Shi-cheng
%A SUN Li-guang
%J Journal of Zhejiang University SCIENCE B
%V 8
%N 6
%P 422~427
%@ 1673-1581
%D 2007
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.2007.B0422

T1 - Effect of lead on ERK activity and the protective function of bFGF in rat primary culture astroglia
A1 - ZHANG Ying
A1 - YE Li-ping
A1 - WANG Biao
A1 - CAO Shi-cheng
A1 - SUN Li-guang
J0 - Journal of Zhejiang University Science B
VL - 8
IS - 6
SP - 422
EP - 427
%@ 1673-1581
Y1 - 2007
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.2007.B0422

Objective: To observe the effects of lead on levels of phosphorylated extracellular signal regulated kinase (p-ERK) in the cytoplasm of primary cultures of rat astroglial cells and the possible protective effect of basic fibroblast growth factor (bFGF) on lead-induced effects. Methods: The primary astroglia cells from 1~6 d old Wistar rats were cultured. The cells pretreated with the MEK1 (mitogen-activated protein kinase kinase 1) inhibitor PD98059 and bFGF, respectively, were exposed to Pb acetate of different concentrations for different times. Western blotting and reverse transcription polymerase chain reaction (RT-PCR) methods were used to detect the protein and mRNA expressions of ERK. Results: mRNA expression for ERK peaked 15 min after initiation of lead exposure (P<0.05) and protein expression of p-ERK peaked at 30 min (P<0.05). ERK mRNA levels and p-ERK protein levels returned to baseline after 60 and 120 min of lead exposure, respectively (P>0.05). The increase in p-ERK levels in lead-treated cells could be inhibited by PD098059. Activation of ERK in the cells by lead was prevented by pretreatment with bFGF. Total ERK protein levels did not change under the same experimental conditions (P>0.05). Conclusion: Low-level lead exposure resulted in transient activation of ERK through the MEK pathway, which then returned to basal levels in the continued presence of lead. Exogenous bFGF protected ERK signaling components in astroglia from lead poisoning.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1] Adams, J.P., Sweatt, J.D., 2002. Molecular psychology: roles for the ERK MAP kinase cascade in memory. Annu. Rev. Pharmacol. Toxicol., 42(1):135-163.

[2] Basilico, C., Moscatelli, D., 1992. The FGF family of growth factors and oncogenes. Adv. Cancer Res., 59:115-165.

[3] Bradbury, M.W., Deane, R., 1993. Permeability of the blood-brain barrier to lead. Neurotoxicology, 14(2-3):131-136.

[4] Chang, L., Karin, M., 2001. Mammalian MAP kinase signaling cascades. Nature, 410(6824):37-40.

[5] Cui, Y., Zhu, Y.G., Zhai, R., Huang, Y., Qiu, Y., Liang, J., 2005. Exposure to metal mixtures and human health impacts in a contaminated area in Nanning, China. Environ. Int., 31(6):784-790.

[6] Dhandapani, K.M., Khan, M.M., Wade, F.M., Wakade, C., Mahesh, V.B., Brann, D.W., 2007. Induction of transforming growth factor-beta1 by basic fibroblast growth factor in rat C6 glioma cells and astrocytes is mediated by MEK/ERK signaling and AP-1 activation. J. Neurosci. Res., 85(5):1033-1045.

[7] Ensoli, B., Markham, P., Kao, V., Barillari, G., Fiorelli, V., Gendelman, R., Raffeld, M., Zon, G., Gallo, R.C., 1994. Block of AIDS-Kaposi’s sarcoma (KS) cell growth, angiogenesis, and lesion formation in nude mice by antisense oligonudeotide targeting basic fibroblast growth factor. A novel strategy for the therapy of KS. J. Clin. Invest., 94(5):1736-1746.

[8] Exkenstien, F.P., 1994. Fibroblast growth factors in the nervous system. J. Neurobio., 25(11):1467-1480.

[9] Kanterewicz, B.I., Urban, N.N., McMahon, D.B., Norman, E.D., Giffen, L.J., Favata, M.F., Scherle, P.A., Trzskos, J.M., Barrionuevo, G., Klann, E., 2000. The extracellular signal regulated kinase cascade is required for NMDA receptor in dependent LTP in area CA1 but not area CA3 of the hippocampus. J. Neurosci., 20(9):3057-3066.

[10] Kolch, W., 2000. Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions. Biochem. J., 351(2):289-305.

[11] Lin, Y.W., Chuang, S.M., Yang, J.L., 2003. Persistent activation of ERK1/2 by lead acetate increases nucleotide excision repair synthesis and confers anti-cytotoxicity and anti-mutagenicity. Carcinogenesis, 24(1):53-61.

[12] Lindahl, L.S., Bird, L., Legare, M.E., Mikeska, G., Bratton, G.R., Tiffany-Castiglioni, E., 1999. Differential ability of astroglia and neuronal cells to accumulate lead: dependence on cell type and on degree of differentiation. Toxicol. Sci., 50(2):236-243.

[13] Mir, A.H., Christopher, M.L.B., Jonathan, P., John, L., 2000. Induction of vascular endothelial growth factor in human astrocytes by lead. J. Biol. Chem., 275(36):27874-27882.

[14] Neben, K., Moehler, T., Egerer, G., Kraemer, A., Hillengass, J., Benner, A., Ho, A.D., Goldschmidt, H., 2001. High plasma basic fibroblast growth factor concentration is associated with response to thalidomide in progressive multiple myeloma. Clin. Cancer Res., 7(9):2675-2681.

[15] Nebreda, A.R., Porras, A., 2000. p38 MAP kinases: beyond the stressresponse. Trends Biochem. Sci., 25(6):257-260.

[16] Qian, Y., Harris, E.D., Zheng, Y., Tiffany-Castiglioni, E., 2000. Lead targets GRP78, a molecular chaperone, in C6 rat glioma cells. Toxicol. Appl. Pharmacol., 163(3):260-266.

[17] Sierra, E.M., Tiffany-Castiglioni, E., 1991. Reduction of glutamine synthetase activity in astroglia exposed in culture to low levels of inorganic lead. Toxicology, 65(3):295-304.

[18] Spence, J.R., Madhavan, M., Aycinena, J.C., Del Rio-Tsonis, K., 2007. Retina regeneration in the chick embryo is not induced by spontaneous Mitf downregulation but requires FGF/FGFR/MEK/Erk dependent upregulation of Pax6. Mol. Vis., 24(13):57-65.

[19] Suresh, C., Dennis, A.O., Heinz, J., Vemuri, M.C., Chetty, C.S., 2006. Melatonin protection against lead-induced changes in human neruoblastoma cell cultures. Int. J. Toxicol., 25(6):459-464.

[20] Tiffany-Castiglioni, E., 1993. Cell culture models for lead toxicity in neuronal and glial cells. Neurotoxicology, 14(4):513-536.

[21] Whitmarsh, A.J., Davis, R.J., 2000. Regulation of transcription factor function by phosphorylation. Cell. Mol. Life Sci., 57(8-9):1172-1183.

[22] Zhu, Z.W., Yang, R.L., Dong, G.J., Zhao, Z.Y., 2005. Study on the neurotoxic effects of low-level lead exposure in rats. J. Zhejiang Univ. Sci. B, 6(7):686-692.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - Journal of Zhejiang University-SCIENCE