ArticleThe Journal of biological chemistry2012
NAD+ levels control Ca2+ store replenishment and mitogen-induced increase of cytosolic Ca2+ by Cyclic ADP-ribose-dependent TRPM2 channel gating in human T lymphocytes.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 64 citations in OpenAlex.
- Review
- scRNA-seq and bulk RNA-seq reveal the characteristics of macrophage copper metabolism and establish a risk signature in hepatocellular carcinoma.Translational cancer research · 2026Article
- Nicotinamide riboside enhances adoptive T cell therapy by promoting memory differentiation and metabolic fitness.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Cold Atmospheric Pressure Plasma-Activated Medium Modulates Cellular Functions of Human Mesenchymal Stem/Stromal Cells In Vitro.International journal of molecular sciences · 2024Article
- Boosting NAD+ levels through fasting to aid in COVID-19 recovery.Frontiers in immunology · 2024Article
- Alterations in the CD56International journal of molecular sciences · 2023Article
- NADCell & bioscience · 2023Review
- Nicotinamide adenine dinucleotide metabolism in the immune response, autoimmunity and inflammageing.British journal of pharmacology · 2022Review
- Interferon-stimulated gene products as regulators of central carbon metabolism.The FEBS journal · 2021Article
- New Insights on the Role of TRP Channels in Calcium Signalling and Immunomodulation: Review of Pathways and Implications for Clinical Practice.Clinical reviews in allergy & immunology · 2021Review
- Distribution and Assembly of TRP Ion Channels.Advances in experimental medicine and biology · 2021Article
- TRPM Channels in Human Diseases.Cells · 2020Review
- Identification, Purification and Molecular Characterization of Chondrosin, a New Protein with Anti-tumoral Activity from the Marine SpongeMarine drugs · 2020Article
- A Review of the Recent Advances Made with SIRT6 and its Implications on Aging Related Processes, Major Human Diseases, and Possible Therapeutic Targets.Biomolecules · 2018Review
- Targeting TRPM2 in ROS-Coupled Diseases.Pharmaceuticals (Basel, Switzerland) · 2016Review
- Mechanistic study of TRPM2-Ca(2+)-CAMK2-BECN1 signaling in oxidative stress-induced autophagy inhibition.Autophagy · 2016Article
- Transient Receptor Potential (TRP) channels in T cells.Seminars in immunopathology · 2016Review
- What is the evidence for the role of TRP channels in inflammatory and immune cells?British journal of pharmacology · 2016Review
- Exogenous NAD(+) administration significantly protects against myocardial ischemia/reperfusion injury in rat model.American journal of translational research · 2016Article
- Preferential Coupling of the NAADP Pathway to Exocytosis in T-Cells.Messenger (Los Angeles, Calif. : Print) · 2015Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intracellular NAD(+) levels ([NAD(+)](i)) are important in regulating human T lymphocyte survival, cytokine secretion, and the capacity to respond to antigenic stimuli. NAD(+)-derived Ca(2+)-mobilizing second messengers, produced by CD38, play a pivotal role in T cell activation. Here we demonstrate that [NAD(+)](i) modifications in T lymphocytes affect intracellular Ca(2+) homeostasis both in terms of mitogen-induced [Ca(2+)](i) increase and of endoplasmic reticulum Ca(2+) store replenishment. Lowering [NAD(+)](i) by FK866-mediated nicotinamide phosphoribosyltransferase inhibition decreased the mitogen-induced [Ca(2+)](i) rise in Jurkat cells and in activated T lymphocytes. Accordingly, the Ca(2+) content of thapsigargin-sensitive Ca(2+) stores was greatly reduced in these cells in the presence of FK866. When NAD(+) levels were increased by supplementing peripheral blood lymphocytes with the NAD(+) precursors nicotinamide, nicotinic acid, or nicotinamide mononucleotide, the Ca(2+) content of thapsigargin-sensitive Ca(2+) stores as well as cell responsiveness to mitogens in terms of [Ca(2+)](i) elevation were up-regulated. The use of specific siRNA showed that the changes of Ca(2+) homeostasis induced by NAD(+) precursors are mediated by CD38 and the consequent ADPR-mediated TRPM2 gating. Finally, the presence of NAD(+) precursors up-regulated important T cell functions, such as proliferation and IL-2 release in response to mitogens.
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