三丁基锡对小鼠脾、肝和脑组织蛋白磷酸酶2A活性的影响

doi:10.3969/j.issn.1004-616x.2013.03.007

癌变·畸变·突变

三丁基锡对小鼠脾、肝和脑组织蛋白磷酸酶2A活性的影响

张亚莉,孙玉涛,翁登坡,徐立红*

( 浙江大学医学院生物化学与遗传学系，浙江杭州 310058 )

收稿日期:2012-03-05 修回日期:2012-05-23 出版日期:2013-05-30 发布日期:2013-05-30
通讯作者: 徐立红，Tel: 0571-88208265，E-mail: xulihong@ zju.edu.cn
作者简介: 张亚莉(1978- )，女，甘肃省渭源县人，博士，研究方向：生化毒理学。E-mail: zyl031912@163.com
基金资助:
国家自然科学基金项目(20777067)

The effects of tributyltin on PP2A activity in mouse spleens, livers and brains

ZHANG Ya-li，SUN Yu-tao，WENG Deng-po，XU Li-hong*

(Department of Biochemistry and Genetics, School of Medicine, Zhejiang University, Hangzhou 310058, Zhejiang, China)

Received:2012-03-05 Revised:2012-05-23 Online:2013-05-30 Published:2013-05-30
Contact: XU Li-hong，Tel: 0571-88208265，E-mail: xulihong@ zju.edu.cn

摘要/Abstract

摘要：

目的：研究三丁基锡 (tributyltin，TBT)对小鼠脾、肝和脑组织蛋白磷酸酶2A (protein phosphatase 2A，PP2A)活性的影响。方法：将不同浓度TBT (0、10、20、60 mg/kg)，分别以灌胃的方式对小鼠染毒24和96 h，检测脾、肝和脑组织PP2A酶活性的改变。结果：TBT染毒24和96 h，小鼠脾脏PP2A酶活性在20和60 mg/kg剂量组明显下降，与对照组相比差异均具有统计学意义 (P < 0.01)；肝脏PP2A酶活性仅在60 mg/kg时，较对照组明显被抑制 (P < 0.05)；而脑PP2A酶活性在各浓度组与对照组相比均未发生明显改变 (P>0.05)。结论：PP2A酶活性的降低可能是TBT产生免疫和肝毒性效应的重要分子机制。

关键词: 三丁基锡, 蛋白磷酸酶2A, 脾, 肝, 脑

Abstract:

OBJECTIVE: To investigate the effects of tributyltin(TBT) on the activity of protein phosphatase 2A(PP2A) in the mouse spleens，livers and brains. METHODS：Mice were orally dosed with 0，10，20 and 60 mg/kg of body weight TBT for 24 h and 96 h，and the activity of PP2A was assessed in the mouse spleens，livers，and brains. RESULTS：PP2A activity in the spleens was obviously inhibited in 20 and 60 mg/kg groups treated for 24 h and 96 h compared to the control group (P< 0.01). PP2A activity in the livers was significantly inhibited in the highest dose of TBT (60 mg/kg) for 96 h compared to the control group (P < 0.05). With regard to the PP2A activity in the brains，there were no statistical significance differences between the control and treatment groups (P>0.05). CONCLUSION：This study suggests a critical role of PP2A in the TBT immunologic and hepatic toxicity mechanisms.

Key words: tributyltin, PP2A, spleens, livers, brains

张亚莉,孙玉涛,翁登坡,徐立红. 三丁基锡对小鼠脾、肝和脑组织蛋白磷酸酶2A活性的影响[J]. 癌变·畸变·突变, doi: 10.3969/j.issn.1004-616x.2013.03.007.

ZHANG Ya-li，SUN Yu-tao，WENG Deng-po，XU Li-hong. The effects of tributyltin on PP2A activity in mouse spleens, livers and brains[J]. Carcinogenesis, Teratogenesis & Mutagenesis, doi: 10.3969/j.issn.1004-616x.2013.03.007.

参考文献

[1] Graceli JB，Sena GC，Lopes PF，et al. Organotins：a review of their reproductive toxicity，biochemistry，and environmental fate [J]. Reprod Toxicol，2012，36 (1) ：40-52.

[2] Gupta M，Dwivedi UN，Khandelwal S. C-Phycocyanin：An effective protective agent against thymic atrophy by tributyltin [J]. Toxicol Lett，2011，204 (1)：2-11.

[3] Dudimah FD，Griffey D，Wang X，et al. Activation of p44/42 MAPK plays a role in the TBT-induced loss of human natural killer (NK) cell function[J]. Cell Biol Toxicol，2010，26 (5)： 435-444.

[4] Ishihara Y，Kawami T，Ishida A，et al. Tributyltin induces oxidative stress and neuronal injury by inhibiting glutathione S-transferase in rat organotypic hippocampal slice cultures [J]. Neurochem Int，2012，60 (8)：782-790.

[5] Nakatsu Y，Kotake Y，Takai N，et al. Involvement of autophagy via mammalian target of rapamycin (mTOR) inhibition in tributyltin-induced neuronal cell death[J]. J Toxicol Sci， 2010，35 (2)：245-251.

[6] Zuo Z，Chen S，Wu T，et al. Tributyltin causes obesity and hepatic steatosis in male mice[J]. Environ Toxicol，2011，26 (1)：79-85.

[7] Grondin M，Marion M，Denizeau F，et al. Tributyltin induces apoptotic signaling in hepatocytes through pathways involving the endoplasmic reticulum and mitochondria[J]. Toxicol Appl Pharmacol，2007，222 (1)：57-68.

[8] Liu HG，Wang Y，Lian L，et al. Tributyltin induces DNA damage as well as oxidative damage in rats [J]. Environ Toxicol，2006， 21 (2)：166-171.

[9] Liu H，Guo Z，Xu L，et al. Protective effect of green tea polyphenols on tributyltin-induced oxidative damage detected by in vivo and in vitro models [J]. Environ Toxicol，2008，23 (1)： 77-83.

[10] Liu HG，Xu LH. Garlic oil prevents tributyltin-induced oxidative damage in vivo and in vitro[J]. J Food Prot，2007，70 (3)： 716-721.

[11] Zhang Y，Liang J，Sun L，et al. Inhibition of PP2A and the consequent activation of JNK/c-Jun are involved in tributyltin-induced apoptosis in human amnionic cells[J]. Environ Toxicol， 2011. doi：10.1002/tox.20730.

[12] Zhang Y，Chen Y，Liang J，et al. Protein phosphatases 2A as well as reactive oxygen species involved in tributyltin-induced apoptosis in mouse livers[J]. Environ Toxicol，2012. doi： 10.1002/tox.21751.

[13] Chen L，Liu L，Huang S. Cadmium activates the mitogen activated protein kinase (MAPK) pathway via induction of reactive oxygen species and inhibition of protein phosphatases 2A and 5[J]. Free Radic Biol Med，2008，45 (7)：1035-1044.

[14] Chen L，Liu L，Yin J，et al. Hydrogen peroxide-induced neuronal apoptosis is associated with inhibition of protein phosphatase 2A and 5，leading to activation of MAPK pathway[J]. Int J Biochem Cell Biol，2009，41 (6)：1284-1295.

[15] Kalev P，Simicek M，Vazquez I，et al. Loss of PPP2R2A inhibits homologous recombination DNA repair and predicts tumor sensitivity to PARP inhibition[J]. Cancer Res，2012，72 (24)：6414-6424.

[16] Yoon SY，Choi JE，Choi JM，et al. Dynein cleavage and microtubule accumulation in okadaic acid-treated neurons[J]. Neurosci Lett，2008，437 (2)：111-115.

[17] Tar K，Csortos C，Czikora I，et al. Role of protein phosphatase 2A in the regulation of endothelial cell cytoskeleton structure [J]. J Cell Biochem，2006，98 (4)：931-953.

[18] Janssens V，Rebollo A. The role and therapeutic potential of Ser/Thr phosphatase PP2A in apoptotic signalling networks in human cancer cells [J]. Curr Mol Med，2012，12 (3)：268-287.

[19] Deng X，Gao F，May WS. Protein phosphatase 2A inactivates Bcl2's antiapoptotic function by dephosphorylation and up-regulation of Bcl-2-p53 binding[J]. Blood ，2009，113 (2)： 422-428.

[20] Boyer IJ. Toxicity of dibutyltin，tributyltin and other organotin compounds to humans and to experimental animals[J]. Toxicology， 1989，55 (3)：253–298.

[21] Gennari A，Viviani B，Galli CL，et al. Organotins induce apoptosis by disturbance of [Ca (2+)] (i) and mitochondrial activity，causing oxidative stress and activation of caspases in rat thymocytes[J]. Toxicol Appl Pharmacol，2000，169 (2)： 185-190.

[22] Bissonnette SL，Haas A，Mann KK，et al. The role of CaMKII in calcium-activated death pathways in bone marrow B cells[J]. Toxicol Sci，2010，118 (1)：108-118.

[23] Tada-Oikawa S，Kato T，Kuribayashi K，et al. Critical role of hydrogen peroxide in the differential susceptibility of Th1 and Th2 cells to tributyltin-induced apoptosis[J]. Biochem Pharmacol， 2008，75 (2)：552-561.

[24] Trotta R，Ciarlariello D，Dal Col J，et al. The PP2A inhibitor SET regulates natural killer cell IFN-gamma production[J]. J Exp Med，2007，204 (10)：2397-2405.

[25] Howe CJ，LaHair MM，McCubrey JA，et al. Redox regulation of the calcium/calmodulin-dependent protein kinases[J]. J Biol Chem，2004，279 (43)：44573-44581.

[26] Nakatsu Y，Kotake Y，Komasaka K，et al. Glutamate excitotoxicity is involved in cell death caused by tributyltin in cultured rat cortical neurons [J]. Toxicol Sci，2006，89 (1)： 235-242.

[27] Nakatsu Y，Kotake Y，Hino A，et al. Activation of AMP-activated protein kinase by tributyltin induces neuronal cell death [J]. Toxicol Appl Pharmacol，2008，230 (3)：358-363.

[28] Wu Y，Song P，Xu J，et al. Activation of protein phosphatase 2A by palmitate inhibits AMP-activated protein kinase[J]. J Biol Chem，2007，282 (13)：9777-9788.

三丁基锡对小鼠脾、肝和脑组织蛋白磷酸酶2A活性的影响

The effects of tributyltin on PP2A activity in mouse spleens, livers and brains

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