缺氧对星形胶质细胞来源的外泌体释放的双刃剑效应。

IF 2.8 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Experimental Biology and Medicine Pub Date : 2025-05-21 eCollection Date: 2025-01-01 DOI:10.3389/ebm.2025.10559
Yang Jie Tseng, Hui-Ju Huang, Chien-Hui Lin, Anya Maan-Yuh Lin
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引用次数: 0

摘要

外泌体是细胞分泌的最小的细胞外囊泡,携带不同的货物,包括核酸、蛋白质和其他从细胞转移到细胞的物质。外泌体的性质取决于供体细胞。缺氧,指的是亚致死和氧气供应不足,据报道会影响缺氧细胞的外泌体分泌。在本研究中,我们重点研究了缺氧对CTX-TNA2星形胶质细胞外泌体的影响,这些细胞暴露于不同的缺氧持续时间,然后作为缺氧预处理的模型。为了评估外泌体的功能,用一种强效神经毒素血红蛋白处理原代培养的皮质神经元。我们的硫代丹胺B实验显示,hemin (30 μM)持续诱导神经元死亡。CTX-TNA2细胞的外泌体接受2小时缺氧+ 6小时缺氧(2H/6R外泌体),而不是12小时缺氧+ 24小时缺氧(12H/24R外泌体)共孵育,可减轻血红素诱导的细胞死亡和生长相关蛋白43水平的降低(神经突起生长的生物标志物)。Western blot检测表明,2H/6R外泌体可减弱血红素诱导的诱导型一氧化氮合酶(iNOS)和环氧合酶-2 (COX-2)水平(两种促炎生物标志物)以及血红素加氧酶-1 (HO-1)的升高。相比之下,12H/24R外泌体没有改变血红素诱导的HO-1升高,但进一步增强了血红素诱导的iNOS和COX-2升高。此外,2H/6R外泌体减弱了血红素诱导的谷胱甘肽氢过氧化物酶4(铁凋亡的生物标志物)的减少和活性半胱天蛋白酶3(凋亡的生物标志物)的升高,而12H/24R外泌体没有有效地改变血红素诱导的程序性细胞死亡。综上所述,我们的研究表明2H/6R外泌体具有神经保护活性,而12H/24R外泌体具有轻度促炎活性,表明不同的缺氧预处理影响CTX-TNA2细胞,从而分泌具有不同生物活性的外泌体。这些发现强调了缺氧对外泌体功能的双刃剑作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A double-edged effect of hypoxia on astrocyte-derived exosome releases.

Exosomes are the smallest extracellular vesicles secreted from cells, carrying different cargos, including nucleic acids, proteins and others which transfer from cells to cells. The properties of exosomes depend on the donor cells. Hypoxia, referring to a sublethal and insufficient oxygen supply, reportedly influences exosome secretion of hypoxic cells. In the present study, we focused on the effects of hypoxia on exosomes obtained from CTX-TNA2 astrocyte cells exposed to different durations of hypoxia followed by normoxia as a model of hypoxic preconditioning. To evaluate the functions of exosomes, primary cultured cortical neurons were treated with hemin, a potent neurotoxin. Our sulforhodamine B assay showed that incubation of hemin (30 μM) consistently induced neuronal death. Co-incubation of exosomes from CTX-TNA2 cells subjected to 2 hr-hypoxia plus 6 hr-renormoxia (2H/6R exosomes), but not 12 hr-hypoxia plus 24 hr-renormoxia (12H/24R exosomes), attenuated hemin-induced cell death and reduction in growth associated protein 43 level (a biomarker of neurite outgrowth). Western blot assay demonstrated that 2H/6R exosomes attenuated hemin-induced elevations in inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) levels (two proinflammatory biomarkers) as well as heme oxygenase-1 (HO-1). In contrast, 12H/24R exosomes did not alter hemin-induced elevation in HO-1 but further augmented hemin-induced increases in iNOS and COX-2. Moreover, 2H/6R exosomes attenuated hemin-induced reduction in glutathione hydroperoxidase 4 (a biomarker of ferroptosis) and elevation in active caspase 3 (a biomarker of apoptosis) while 12H/24R exosomes did not effectively alter hemin-induced programed cell death. In conclusion, our study showed that 2H/6R exosomes possessed neuroprotective activities while 12H/24R exosomes had mild pro-inflammatory activities, suggesting that different hypoxic preconditionings influenced CTX-TNA2 cells which then secreted exosomes with differential biological activities. These findings highlight a double-edged role of hypoxia on exosome functions.

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来源期刊
Experimental Biology and Medicine
Experimental Biology and Medicine 医学-医学:研究与实验
CiteScore
6.00
自引率
0.00%
发文量
157
审稿时长
1 months
期刊介绍: Experimental Biology and Medicine (EBM) is a global, peer-reviewed journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences. EBM provides both research and review articles as well as meeting symposia and brief communications. Articles in EBM represent cutting edge research at the overlapping junctions of the biological, physical and engineering sciences that impact upon the health and welfare of the world''s population. Topics covered in EBM include: Anatomy/Pathology; Biochemistry and Molecular Biology; Bioimaging; Biomedical Engineering; Bionanoscience; Cell and Developmental Biology; Endocrinology and Nutrition; Environmental Health/Biomarkers/Precision Medicine; Genomics, Proteomics, and Bioinformatics; Immunology/Microbiology/Virology; Mechanisms of Aging; Neuroscience; Pharmacology and Toxicology; Physiology; Stem Cell Biology; Structural Biology; Systems Biology and Microphysiological Systems; and Translational Research.
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