کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1933739 | 1050623 | 2009 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
An anti-apoptotic peptide improves survival in lethal total body irradiation
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Cell penetrating peptides (CPPs) have been used to deliver the anti-apoptotic Bcl-xL-derived BH4 peptide to prevent injury-induced apoptosis both in vitro and in vivo. Here we demonstrate that the nuclear localization sequence (NLS) from the SV40 large T antigen has favorable properties for BH4 domain delivery to lymphocytes compared to sequences based on the HIV-1 TAT sequence. While both TAT-BH4 and NLS-BH4 protected primary human mononuclear cells from radiation-induced apoptotic cell death, TAT-BH4 caused persistent membrane damage and even cell death at the highest concentrations tested (5-10 μM) and correlated with in vivo toxicity as intravenous administration of TAT-BH4 caused rapid death. The NLS-BH4 peptide has significantly attenuated toxicity compared to TAT-BH4 and we established a dosing regimen of NLS-BH4 that conferred a significant survival advantage in a post-exposure treatment model of LD90 total body irradiation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 382, Issue 4, 15 May 2009, Pages 657-662
Journal: Biochemical and Biophysical Research Communications - Volume 382, Issue 4, 15 May 2009, Pages 657-662
نویسندگان
Jonathan E. McDunn, Jared T. Muenzer, Benjamin Dunne, Anthony Zhou, Kevin Yuan, Andrew Hoekzema, Carolyn Hilliard, Katherine C. Chang, Christopher G. Davis, Jacquelyn McDonough, Clayton Hunt, Perry Grigsby, David Piwnica-Worms, Richard S. Hotchkiss,