A novel cell-penetrating peptide protects against neuron apoptosis after cerebral ischemia by inhibiting the nuclear translocation of annexin A1.

Cell Death and Differentiation
Xing LiJing Shi

Abstract

Nuclear translocation of annexin A1 (ANXA1) has recently been reported to participate in neuronal apoptosis after cerebral ischemia. Prevention of the nuclear translocation of ANXA1 should therefore inhibit neuronal apoptosis and protect against cerebral stroke. Here, we found that, in the repeat III domain of ANXA1, the amino-acid residues from R228 to F237 function as a unique nuclear translocation signal (NTS) and are required for nuclear translocation of ANXA1. Intriguingly, we synthesized a cell-penetrating peptide derived by conjugating the trans-activator of transcription (Tat) domain to the NTS sequence. This Tat-NTS peptide specifically blocked the interaction of ANXA1 with importin β and, consequently, the nuclear translocation of ANXA1 without affecting the nucleocytoplasmic shuttling of other proteins. The Tat-NTS peptide inhibited the transcriptional activity of p53, decreased Bid expression, suppressed activation of the caspase-3 apoptosis pathway and improved the survival of hippocampal neurons subjected to oxygen-glucose deprivation and reperfusion in vitro. Moreover, using a focal brain ischemia animal model, we showed that the Tat-NTS peptide could be efficiently infused into the ischemic hippocampus and corte...Continue Reading

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Citations

Mar 6, 2021·Molecular Therapy. Methods & Clinical Development·Jing LuoYin Zhao
Apr 4, 2021·International Journal of Molecular Sciences·Thomas GrewalUrsula Rescher
Mar 24, 2021·Cardiovascular Research·Changping ZhouLemin Zheng

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Methods Mentioned

BETA
nuclear translocation
fluorescence microscopy
Co-IP
nuclear
PCR
dissection
fluorescence assay
transfections
protein assay
electrophoresis

Software Mentioned

GraphPad Prism
GraphPad
Pro Plus
Image

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