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The humanin peptide mediates ELP nanoassembly and protects human retinal pigment epithelial cells from oxidative stress.
Nanomedicine: Nanotechnology, Biology and Medicine ( IF 4.2 ) Pub Date : 2019-10-23 , DOI: 10.1016/j.nano.2019.102111 Zhe Li 1 , Parameswaran G Sreekumar 2 , Santosh Peddi 1 , David R Hinton 3 , Ram Kannan 2 , John Andrew MacKay 4
Nanomedicine: Nanotechnology, Biology and Medicine ( IF 4.2 ) Pub Date : 2019-10-23 , DOI: 10.1016/j.nano.2019.102111 Zhe Li 1 , Parameswaran G Sreekumar 2 , Santosh Peddi 1 , David R Hinton 3 , Ram Kannan 2 , John Andrew MacKay 4
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Humanin (HN) is a hydrophobic 24-amino acid peptide derived from mitochondrial DNA that modulates cellular responses to oxidative stress and protects human retinal pigment epithelium (RPE) cells from apoptosis. To solubilize HN, this report describes two genetically-encoded fusions between HN and elastin-like polypeptides (ELP). ELPs provide steric stabilization and/or thermo-responsive phase separation. Fusions were designed to either remain soluble or phase separate at the physiological temperature of the retina. Interestingly, the soluble fusion assembles stable colloids with a hydrodynamic radius of 39.1 nm at 37°C. As intended, the thermo-responsive fusion forms large coacervates (>1,000 nm) at 37°C. Both fusions bind human RPE cells and protect against oxidative stress-induction of apoptosis (TUNEL, caspase-3 activation). Their activity is mediated through STAT3; furthermore, STAT3 inhibition eliminates their protection. These findings suggest that HN polypeptides may facilitate cellular delivery of biodegradable nanoparticles with potential protection against age-related diseases, including macular degeneration.
中文翻译：
人类素肽介导ELP纳米组装并保护人类视网膜色素上皮细胞免受氧化应激。
Humanin（HN）是一种来自线粒体DNA的疏水性24氨基酸肽，可调节细胞对氧化应激的反应并保护人视网膜色素上皮（RPE）细胞免于凋亡。为了增溶HN，本报告介绍了HN和弹性蛋白样多肽（ELP）之间的两种遗传编码融合。ELP提供空间稳定和/或热响应相分离。融合体被设计为在视网膜的生理温度下保持可溶或相分离。有趣的是，可溶性融合物在37°C时组装的胶体的流体力学半径为39.1 nm。如预期的那样，热响应性融合在37°C时会形成大凝聚层（> 1,000 nm）。两种融合体均结合人RPE细胞，并防止氧化应激诱导的细胞凋亡（TUNEL，caspase-3激活）。它们的活性是通过STAT3介导的。此外，STAT3抑制作用消除了它们的保护作用。这些发现表明，HN多肽可以促进可生物降解的纳米颗粒的细胞递送，并具有针对与年龄相关的疾病（包括黄斑变性）的潜在保护作用。
更新日期：2019-10-24
中文翻译：
人类素肽介导ELP纳米组装并保护人类视网膜色素上皮细胞免受氧化应激。
Humanin（HN）是一种来自线粒体DNA的疏水性24氨基酸肽，可调节细胞对氧化应激的反应并保护人视网膜色素上皮（RPE）细胞免于凋亡。为了增溶HN，本报告介绍了HN和弹性蛋白样多肽（ELP）之间的两种遗传编码融合。ELP提供空间稳定和/或热响应相分离。融合体被设计为在视网膜的生理温度下保持可溶或相分离。有趣的是，可溶性融合物在37°C时组装的胶体的流体力学半径为39.1 nm。如预期的那样，热响应性融合在37°C时会形成大凝聚层（> 1,000 nm）。两种融合体均结合人RPE细胞，并防止氧化应激诱导的细胞凋亡（TUNEL，caspase-3激活）。它们的活性是通过STAT3介导的。此外，STAT3抑制作用消除了它们的保护作用。这些发现表明，HN多肽可以促进可生物降解的纳米颗粒的细胞递送，并具有针对与年龄相关的疾病（包括黄斑变性）的潜在保护作用。
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