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doi:10.22028/D291-33791
Titel: | High glucose attenuates Ca2+ influx in cytotoxic T lymphocytes upon target recognition |
VerfasserIn: | Zou, Huajiao Schwär, Gertrud Zhao, Renping Alansary, Dalia Yin, Deling Schwarz, Eva C. Niemeyer, Barbara Qu, Bin |
Sprache: | Englisch |
Verlag/Plattform: | bioRxiv |
Erscheinungsjahr: | 2020 |
Dokumenttyp: | Sonstiges |
Abstract: | The killing efficiency of cytotoxic T lymphocytes (CTLs) is tightly regulated by intracellular Ca2+ concentration. Glucose is the key energy source for CTLs, lack of which significantly impairs CTL activation, proliferation and effector functions. The impact of high glucose on Ca2+ influx in CTLs remains largely elusive. In this work, we stimulated primary human CD8+ T cells in medium containing either 25 mM (high glucose, HG) or 5.6 mM glucose (normal glucose, NG). We found that store-operated calcium entry (SOCE) induced by thapsigargin (Tg) is elevated in HG-cultured CTLs compared to their counterparts in NG. Unexpectedly, the Ca2+ influx elicited by recognition of target cells is reduced in HG-cultured CTLs. Under HG condition, STIM1 and STIM2, the calcium sensors in the endoplasmic reticulum (ER), were down-regulated; ORAI1, the main structural component of calcium-release activated channels, remained unchanged, whereas ORAI2 and ORAI3 were up-regulated. The fraction of necrosis of HG-cultured CTLs was enhanced after killing without affecting glucose uptake. Thus, our findings reveal that HG has a distinctive impact on Tg-evoked SOCE and target recognition-induced Ca2+ influx in CTLs and causes more CTL death after killing, suggesting a novel regulatory role of high glucose on modulating CTL functions. |
DOI der Erstveröffentlichung: | 10.1101/2020.04.09.028019 |
URL der Erstveröffentlichung: | https://www.biorxiv.org/content/10.1101/2020.04.09.028019v1 |
Link zu diesem Datensatz: | hdl:20.500.11880/32116 http://dx.doi.org/10.22028/D291-33791 |
Datum des Eintrags: | 3-Jan-2022 |
Bemerkung/Hinweis: | Preprint |
Fakultät: | M - Medizinische Fakultät |
Fachrichtung: | M - Biophysik |
Professur: | M - Prof. Dr. Markus Hoth |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
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