PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
The Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase (SERCA) Activator CDN1163 Exerts Complex Time-Dependent and SERCA Isoform-Specific Effects on T Lymphocyte Ca2+ Store Functions
Version 1
: Received: 8 February 2024 / Approved: 9 February 2024 / Online: 9 February 2024 (10:06:51 CET)
How to cite:
Uddin, M.N.; Thomas, D.W. The Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase (SERCA) Activator CDN1163 Exerts Complex Time-Dependent and SERCA Isoform-Specific Effects on T Lymphocyte Ca2+ Store Functions. Preprints2024, 2024020568. https://doi.org/10.20944/preprints202402.0568.v1
Uddin, M.N.; Thomas, D.W. The Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase (SERCA) Activator CDN1163 Exerts Complex Time-Dependent and SERCA Isoform-Specific Effects on T Lymphocyte Ca2+ Store Functions. Preprints 2024, 2024020568. https://doi.org/10.20944/preprints202402.0568.v1
Uddin, M.N.; Thomas, D.W. The Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase (SERCA) Activator CDN1163 Exerts Complex Time-Dependent and SERCA Isoform-Specific Effects on T Lymphocyte Ca2+ Store Functions. Preprints2024, 2024020568. https://doi.org/10.20944/preprints202402.0568.v1
APA Style
Uddin, M.N., & Thomas, D.W. (2024). The Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase (SERCA) Activator CDN1163 Exerts Complex Time-Dependent and SERCA Isoform-Specific Effects on T Lymphocyte Ca2+ Store Functions. Preprints. https://doi.org/10.20944/preprints202402.0568.v1
Chicago/Turabian Style
Uddin, M.N. and David W. Thomas. 2024 "The Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase (SERCA) Activator CDN1163 Exerts Complex Time-Dependent and SERCA Isoform-Specific Effects on T Lymphocyte Ca2+ Store Functions" Preprints. https://doi.org/10.20944/preprints202402.0568.v1
Abstract
The allosteric SERCA (Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase) activator CDN1163 has been recently added to the group of pharmacological tools for probing SERCA function. We chose to investigate the effects of the compound on T lymphocyte Ca2+ stores, using the well-described Jurkat T lymphocyte as a reliable cell system for Ca2+ signaling pathways. Our study identified the lowest concentrations of the SERCA inhibitors thapsigargin (TG) and 2,5-di-(tert butyl)-1,4-benzohydroquinone (tBHQ) capable of releasing Ca2+, permitting the differentiation of the TG-sensitive SERCA 2b Ca2+ store from the tBHQ-sensitive SERCA 3 Ca2+ store. We proceeded to test the effects of CDN1163 on Ca2+ stores, examining specific actions on the SERCA 2b and SERCA 3 Ca2+ pools using our low dose SERCA blocker regimen. In contrast to previous work, we find CDN1163 exerts complex time-sensitive and SERCA isoform-specific actions on Ca2+ stores. Surprisingly, short-term exposure (0-30 minutes) to CDN1163 perturbs T cell Ca2+ stores by suppressing Ca2+ uptake with diminished Ca2+ release from the SERCA 2b-controlled store. Concomitantly, we find evidence for a SERCA-activating effect of CDN1163 on the SERCA 3 regulated store, given the observation of increased Ca2+ release inducible by low dose tBHQ. Intriguingly, longer-term (>12 hours) CDN1163 exposure reversed this pattern, with increased Ca2+ release from SERCA 2b-regulated pools, yet decreased Ca2+ release responses from tBHQ-sensitive SERCA 3 pool. Our results reveal differential effects of CDN1163 on Ca2+ stores regulated by distinct SERCA isoforms, prompting the need for careful interpretation of the compound’s effects, particularly in cells expressing multiple SERCA isoforms.
Keywords
Ca2+ Stores; SERCA Regulation; ER Ca2+ Pools; T Cell Activation
Subject
Biology and Life Sciences, Cell and Developmental Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
