Nucleus-targeted delivery of nitric oxide in human mesenchymal stem cells enhances osteogenic differentiation
- 주제(키워드) Cell-penetrating peptide , Differentiation , Mesenchymal stem cells , Nitric oxide , Nuclear localization signal
- 등재 SCIE, SCOPUS
- 발행기관 Academic Press Inc.
- 발행년도 2023
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000208904
- 본문언어 영어
- Published As https://doi.org/10.1016/j.bioorg.2023.106483
- PubMed 37062230
초록/요약
Nitric oxide (NO) is an important gaseous signaling molecule in various physiological processes, which functions through interactions with its acceptor molecules located in organelles. NO has an extremely short half-life, making it challenging to experimentally achieve effective NO levels in organelles to study these interactions. Here we developed an organelle-specific, peptide-based NO delivery material that targets the nucleus. NO was attached to the SH group of a cysteine residue inserted into the N-terminus of a cell-penetrating peptide (CPP) conjugated to varying repeats of the nuclear localization signal (NLS), which we denoted NO-CysCPP-NLS, through S-nitrosylation. NO-CysCPP-NLS strongly induced osteogenic differentiation of mesenchymal stem cells. This delivery concept can be extended to cells other than stem cells to elucidate the effects of NO release in the nucleus. Furthermore, conjugation of NO to CysCPP fused to mitochondria- or lysosome-targeting signals can be used to deliver NO to other organelles such as mitochondria and lysosomes, respectively. © 2023 Elsevier Inc.
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