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睾丸小管周细胞衰老的蛋白质组学研究——来自非人类灵长类动物模型的启示。

Proteomic Insights into Senescence of Testicular Peritubular Cells from a Nonhuman Primate Model.

机构信息

Laboratory for Functional Genome Analysis LAFUGA, Gene Center, LMU München, 81377 Munich, Germany.

LMU München, Biomedical Center (BMC), Anatomy III-Cell Biology, 82152 Martinsried, Germany.

出版信息

Cells. 2020 Nov 17;9(11):2498. doi: 10.3390/cells9112498.

Abstract

Age-related changes in the human testis may include morphological alterations, disturbed steroidogenesis, and impaired spermatogenesis. However, the specific impact of cell age remains poorly understood and difficult to assess. Testicular peritubular cells fulfill essential functions, including sperm transport, contributions to the spermatogonial stem cell niche, and paracrine interactions within the testis. To study their role in age-associated decline of testicular functions, we performed comprehensive proteome and secretome analyses of repeatedly passaged peritubular cells from . This nonhuman primate model better reflects the human testicular biology than rodents and further gives access to young donors unavailable from humans. Among 5095 identified proteins, 583 were differentially abundant between samples with low and high passage numbers. The alterations indicate a reduced ability of senescent peritubular cells to contract and secrete proteins, as well as disturbances in nuclear factor (NF)-κB signaling and a reduced capacity to handle reactive oxygen species. Since this in vitro model may not exactly mirror all molecular aspects of in vivo aging, we investigated the proteomes and secretomes of testicular peritubular cells from young and old donors. Even though the age-related alterations at the protein level were less pronounced, we found evidence for impaired protein secretion, altered NF-κB signaling, and reduced contractility of these in vivo aged peritubular cells.

摘要

人类睾丸的年龄相关性变化可能包括形态改变、类固醇生成障碍和精子发生受损。然而,细胞年龄的具体影响仍知之甚少,难以评估。睾丸小管周细胞具有重要的功能,包括精子运输、对精原干细胞龛的贡献以及睾丸内的旁分泌相互作用。为了研究它们在与年龄相关的睾丸功能下降中的作用,我们对来自. 的反复传代的小管周细胞进行了全面的蛋白质组和分泌组分析。这种非人类灵长类动物模型比啮齿动物更能反映人类的睾丸生物学,并且可以获得人类无法获得的年轻供体。在鉴定出的 5095 种蛋白质中,有 583 种在低传代和高传代样本之间存在丰度差异。这些变化表明衰老的小管周细胞收缩和分泌蛋白质的能力降低,核因子 (NF)-κB 信号紊乱,以及处理活性氧的能力降低。由于这种体外模型可能无法完全反映体内衰老的所有分子方面,我们研究了年轻和老年供体睾丸小管周细胞的蛋白质组和分泌组。尽管在蛋白质水平上与年龄相关的变化不那么明显,但我们发现这些体内衰老的小管周细胞的蛋白质分泌受损、NF-κB 信号改变和收缩性降低的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/130c/7698562/34bffcfee6f9/cells-09-02498-g0A1.jpg

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