TAT-BH4能降低辐射后的细胞死亡率

生物谷

生物谷报道：美国华盛顿大学（Washington University）医学院的研究人员研发了一种试剂，对受到辐射照射的细胞具有保护作用，此研究发表于四月份的Biochemical and Biophysical Research Communications期刊。由Clayton Hunt博士主导此研究进行。

这个试剂名为TAT-BH4，能轻易的进入细胞中与Bcl-xL蛋白的结合，而Bcl-xL蛋白已知功能为阻断细胞死亡，研究人员以小鼠为试验对象，实验共分为四组，正常组不照辐射，对照组则只照辐射未给予任何药物治疗，另外两组则在辐照30分钟前后分别经由静脉注射给予TAT-BH4，辐照强度为5 Grays，这个强度在人类能造成血球细胞急速下降，导致出血及感染。

研究人员分析了各组小鼠B细胞及T细胞的死亡率，未照辐射的空白组分别为4.7%及5.1%；照射辐射而未给予治疗的组别为15.6%及38.7%；辐射照射前给予TAT-BH4的组别两种白血球细胞死亡率为8.6%及16.9%；辐射照射后再给予TAT-BH4的组别则为5.7%及12.3%。由此结果显示，TAT-BH4能有效保护B细胞及T细胞，避免其走向自然凋亡（apoptosis）的命运，而又以辐射照射后再给予TAT-BH4的保护效应为最好。

(资料来源 : Bio.com)

原始出处:

Biochemical and Biophysical Research Communications
Volume 355, Issue 2, 6 April 2007, Pages 501-507

Anti-apoptotic peptides protect against radiation-induced cell death

Kevin W. McConnella, 1, Jared T. Muenzerb, 1, Kathy C. Changc, Chris G. Davisc, Jonathan E. McDunnc, Craig M. Coopersmitha, c, Carolyn A. Hilliardd, Richard S. Hotchkissa, c, Perry W. Grigsbyd and Clayton R. Huntd, Corresponding Author Contact Information , E-mail The Corresponding Author
aDepartment of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA
bDepartment of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA
cDepartment of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA
dDepartment of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA
Received 30 January 2007. Available online 8 February 2007.

Abstract

The risk of terrorist attacks utilizing either nuclear or radiological weapons has raised concerns about the current lack of effective radioprotectants. Here it is demonstrated that the BH4 peptide domain of the anti-apoptotic protein Bcl-xL can be delivered to cells by covalent attachment to the TAT peptide transduction domain (TAT-BH4) and provide protection in vitro and in vivo from radiation-induced apoptotic cell death. Isolated human lymphocytes treated with TAT-BH4 were protected against apoptosis following exposure to 15 Gy radiation. In mice exposed to 5 Gy radiation, TAT-BH4 treatment protected splenocytes and thymocytes from radiation-induced apoptotic cell death. Most importantly, in vivo radiation protection was observed in mice whether TAT-BH4 treatment was given prior to or after irradiation. Thus, by targeting steps within the apoptosis signaling pathway it is possible to develop post-exposure treatments to protect radio-sensitive tissues.

Keywords: TAT; BH4; Bcl-xL; Apoptosis; Radioprotectants; Lymphocyte

star, open This work was supported by National Institutes of Health Grants GM055194, GM044118, GM008795, GM066202, GM072808, K12HD0085020, and PO1CA104457.
Corresponding Author Contact Information Corresponding author. Fax: +1 314 362 9790.
1 These authors contributed equally to this work