探索MOTS-c在年龄相关性黄斑变性中的治疗潜力:从细胞反应到患者来源的细胞杂交。

IF 3.4 3区 生物学 Q3 CELL BIOLOGY
Zahra Mohtashami, Kevin Schneider, Reza Azimi, Shari Atilano, Marilyn Chwa, M Cristina Kenney, Mithalesh Kumar Singh
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引用次数: 0

摘要

在美国,年龄相关性黄斑变性(AMD)是导致不可逆视力丧失的主要原因,在老年人中呈上升趋势。mtDNA断裂和16S或12S rRNA损伤引起的线粒体来源肽的不受控制可能会加重AMD。我们之前的研究表明Humanin G对视网膜色素上皮细胞(RPE)具有细胞保护作用。然而,作为一种高效的线粒体肽,MOTS-c对视网膜细胞存活的影响尚未得到评价。在这项研究中,我们发现野生型(wt-)和分化的ARPE19细胞(diffi -ARPE19)在作用上存在差异,这意味着细胞分化状态可能会影响细胞对MOTS-c的反应。MOTS-c对diffi - arpe19细胞的凋亡、炎症和线粒体生物发生具有剂量依赖性作用。较低剂量(500 nM)比5µM浓度的影响更显著。在diffi - arpe19细胞中,低剂量的MOTS-c可以减轻缺氧对细胞存活和基因表达的负面影响,包括凋亡(CASP3, CASP9),线粒体生物发生(TFAM, PGC-1α)和代谢传感器(AMPK)。然而,无论MOTS-c剂量如何,对ROS水平或NRF1表达均无显著影响。在化学诱导的缺氧环境中,在治疗前后将不同arpe19细胞暴露于不同剂量的MOTS-c中,与单独使用MOTS-c治疗相比,没有额外的益处。与年龄匹配的对照细胞系相比,MOTS-c对AMD患者细胞凋亡、线粒体生物发生和抗氧化活性相关基因的表达有不同的影响。MOTS-c肽似乎可以增强细胞代谢并调节基因表达,这可能为AMD提供潜在的治疗益处。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Exploring the therapeutic potential of MOTS-c in age-related macular degeneration: from cellular responses to patient-derived cybrids.

Age-related macular degeneration (AMD), the leading cause of irreversible vision loss in the US, is on the rise among the elderly. Uncontrolled mitochondria-derived peptide production from mtDNA disruption and 16S or 12S rRNA damage could worsen AMD. Our previous work has shown that Humanin G possesses cytoprotective effects in retinal pigment epithelial (RPE) cells. However, MOTS-c, a highly efficient mitochondrial peptide, has yet to be evaluated on retinal cell survival. In this study, we show that there are differences in effects between wild-type (wt-) and differentiated ARPE19 cells (diff-ARPE19), implying that the cellular differentiation status may influence how cells respond to MOTS-c. MOTS-c has dose-dependent effects on apoptosis, inflammation, and mitochondrial biogenesis in diff-ARPE19 cells. Lower doses (500 nM) have more significant impacts than 5 µM concentrations. In diff-ARPE19 cells, a lower dose of MOTS-c can reduce the negative impact of hypoxia on cellular survival and gene expression, including apoptosis (CASP3, CASP9), mitochondrial biogenesis (TFAM, PGC-1α), and metabolic sensor (AMPK). However, it had no significant effect on ROS levels or NRF1 expression, regardless of MOTS-c dose. Exposing diff-ARPE19 cells to varied MOTS-c dosages before and after therapy in a chemically induced hypoxic environment yields no extra benefits as compared to MOTS-c treatment alone. MOTS-c had different effects on the expression of genes linked with apoptosis, mitochondrial biogenesis, and antioxidant activity in AMD patients versus age-matched control cybrids. The MOTS-c peptide appears to enhance cellular metabolism and regulate gene expression, which could potentially provide therapeutic benefits in AMD.

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来源期刊
Human Cell
Human Cell CELL BIOLOGY-
CiteScore
5.90
自引率
2.30%
发文量
176
审稿时长
4.5 months
期刊介绍: Human Cell is the official English-language journal of the Japan Human Cell Society. The journal serves as a forum for international research on all aspects of the human cell, encompassing not only cell biology but also pathology, cytology, and oncology, including clinical oncology. Embryonic stem cells derived from animals, regenerative medicine using animal cells, and experimental animal models with implications for human diseases are covered as well. Submissions in any of the following categories will be considered: Research Articles, Cell Lines, Rapid Communications, Reviews, and Letters to the Editor. A brief clinical case report focusing on cellular responses to pathological insults in human studies may also be submitted as a Letter to the Editor in a concise and short format. Not only basic scientists but also gynecologists, oncologists, and other clinical scientists are welcome to submit work expressing new ideas or research using human cells.
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