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人类 T 细胞中药理学端粒酶激活剂的功能评估。

Functional assessment of pharmacological telomerase activators in human T cells.

机构信息

Department of Biology, Whittier College,13406 Philadelphia Street, P.O. Box 634, Whittier 90608, CA, USA.

Department of Pathology and Lab Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles 90095-1732, CA, USA.

出版信息

Cells. 2013 Jan 14;2(1):57-66. doi: 10.3390/cells2010057.

DOI:10.3390/cells2010057
PMID:24709644
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3972662/
Abstract

Telomeres are structures at the ends of chromosomes that shorten during cell division and eventually signal an irreversible state of growth arrest known as cellular senescence. To delay this cellular aging, human T cells, which are critical in the immune control over infections and cancer, activate the enzyme telomerase, which binds and extends the telomeres. Several different extracts from the Astragalus membranaceus root have been documented to activate telomerase activity in human T cells. The objective of this research was to compare two extracts from Astragalus membranaceus, TA-65 and HTA, for their effects on both telomerase and proliferative activity of human CD4 and CD8 T cells. Our results demonstrate that, TA-65 increased telomerase activity significantly (1.3 to 3.3-fold relative to controls) in T cell cultures from six donors tested, whereas HTA only increased telomerase levels in two out of six donors. We also demonstrate that TA-65 activates telomerase by a MAPK- specific pathway. Finally, we determine that during a three-day culture period, only the T cells treated with the TA-65 extract showed a statistically significant increase in proliferative activity. Our results underscore the importance of comparing multiple telomerase activators within the same experiment, and of including functional assays in addition to measuring telomerase activity.

摘要

端粒是染色体末端的结构,在细胞分裂过程中会缩短,最终导致不可逆的生长停滞状态,即细胞衰老。为了延缓这种细胞衰老,在感染和癌症的免疫控制中至关重要的人类 T 细胞激活端粒酶,端粒酶结合并延长端粒。已经有文献记录,从黄芪根中提取的几种不同提取物可以激活人类 T 细胞中的端粒酶活性。本研究的目的是比较两种黄芪提取物 TA-65 和 HTA 对人 CD4 和 CD8 T 细胞端粒酶活性和增殖活性的影响。我们的结果表明,在 6 位供体的 T 细胞培养物中,TA-65 显著增加了端粒酶活性(相对于对照增加了 1.3 至 3.3 倍),而 HTA 仅在 6 位供体中的两位增加了端粒酶水平。我们还证明 TA-65 通过 MAPK 特异性途径激活端粒酶。最后,我们确定在为期三天的培养期间,仅用 TA-65 提取物处理的 T 细胞显示出增殖活性的统计学显著增加。我们的结果强调了在同一个实验中比较多个端粒酶激活剂的重要性,并且除了测量端粒酶活性之外,还包括功能测定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f4b/3972662/7cf5f0c7dfbb/cells-02-00057-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f4b/3972662/145357337556/cells-02-00057-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f4b/3972662/8b6cf66cd6a1/cells-02-00057-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f4b/3972662/e75fa1dc1d63/cells-02-00057-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f4b/3972662/7cf5f0c7dfbb/cells-02-00057-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f4b/3972662/145357337556/cells-02-00057-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f4b/3972662/8b6cf66cd6a1/cells-02-00057-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f4b/3972662/e75fa1dc1d63/cells-02-00057-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f4b/3972662/7cf5f0c7dfbb/cells-02-00057-g004.jpg

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3
Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice.
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RSC Adv. 2023 May 15;13(22):14855-14862. doi: 10.1039/d3ra01229h.
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