Characterisation of neuroprotective efficacy of modified poly-arginine-9 (R9) peptides using a neuronal glutamic acid excitotoxicity model
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- 作者：Adam B. Edwards ; Ryan S. Anderton…
- 关键词：Poly ; arginine peptides ; Arginine ; rich peptides ; Cortical neurons ; Neuroprotection ; Glutamate excitotoxicity ; Cortical neurons ; Cell ; penetrating peptides
- 刊名：Molecular and Cellular Biochemistry
- 出版年：2017
- 出版时间：February 2017
- 年：2017
- 卷：426
- 期：1-2
- 页码：75-85
- 全文大小：
- 刊物类别：Biomedical and Life Sciences
- 刊物主题：Biochemistry, general; Medical Biochemistry; Oncology; Cardiology;
- 出版者：Springer US
- ISSN：1573-4919
- 卷排序：426
文摘
In a recent study, we highlighted the importance of cationic charge and arginine residues for the neuroprotective properties of poly-arginine and arginine-rich peptides. In this study, using cortical neuronal cultures and an in vitro glutamic acid excitotoxicity model, we examined the neuroprotective efficacy of different modifications to the poly-arginine-9 peptide (R9). We compared an unmodified R9 peptide with R9 peptides containing the following modifications: (i) C-terminal amidation (R9-NH2); (ii) N-terminal acetylation (Ac-R9); (iii) C-terminal amidation with N-terminal acetylation (Ac-R9-NH2); and (iv) C-terminal amidation with d-amino acids (R9D-NH2). The three C-terminal amidated peptides (R9-NH2, Ac-R9-NH2, and R9D-NH2) displayed neuroprotective effects greater than the unmodified R9 peptide, while the N-terminal acetylated peptide (Ac-R9) had reduced efficacy. Using the R9-NH2 peptide, neuroprotection could be induced with a 10 min peptide pre-treatment, 1–6 h before glutamic acid insult, or when added to neuronal cultures up to 45 min post-insult. In addition, all peptides were capable of reducing glutamic acid-mediated neuronal intracellular calcium influx, in a manner that reflected their neuroprotective efficacy. This study further highlights the neuroprotective properties of poly-arginine peptides and provides insight into peptide modifications that affect efficacy.