ArticlePhilosophical transactions of the Royal Society of London. Series B, Biological sciences2016
Calcium and adenosine triphosphate control of cellular pathology: asparaginase-induced pancreatitis elicited via protease-activated receptor 2.
Article in Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 57 citations in OpenAlex.
- Retrospective analysis of asparaginase-associated pancreatitis in pediatric acute lymphoblastic leukemia: focus on rechallenge with pegaspargase.Journal of cancer research and clinical oncology · 2025Review
- L-asparaginase induces IP3R-mediated ER CaCell death discovery · 2024Article
- Combination of the CRAC Channel Inhibitor CM4620 and Galactose as a Potential Therapy for Acute Pancreatitis.Function (Oxford, England) · 2024Article
- Neutrophil-specific ORAI1 Calcium Channel Inhibition Reduces Pancreatitis-associated Acute Lung Injury.Function (Oxford, England) · 2024Article
- Acute pancreatitis following asparaginase treatment in pediatric acute lymphoblastic leukemia with a heterozygousFrontiers in pediatrics · 2024Article
- The role of CaCell calcium · 2023Review
- Watching Living Cells in Action in the Exocrine Pancreas: The Palade Prize Lecture.Function (Oxford, England) · 2023Review
- Driver Mutations of Pancreatic Cancer Affect CaFunction (Oxford, England) · 2023Article
- The 2022 George E Palade Medal Lecture: Toxic CaPancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2023Review
- Requirement for ER-mitochondria CaFrontiers in cell and developmental biology · 2023Article
- Current Use of Asparaginase in Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma.Frontiers in pediatrics · 2022Review
- The Role of Phosphate in Alcohol-Induced Experimental Pancreatitis.Gastroenterology · 2021Article
- A narrative review of acute pancreatitis and its diagnosis, pathogenetic mechanism, and management.Annals of translational medicine · 2021Review
- Store-Operated Calcium Entry as a Therapeutic Target in Acute Pancreatitis: Discovery and Development of Drug-Like SOCE Inhibitors.Journal of medicinal chemistry · 2020Article
- Intracellular CaInternational journal of molecular sciences · 2020Review
- Bcl-2-Protein Family as Modulators of IPCold Spring Harbor perspectives in biology · 2020Review
- Asparagine Synthetase Is Highly Expressed at Baseline in the Pancreas Through Heightened PERK Signaling.Cellular and molecular gastroenterology and hepatology · 2020Article
- ABT-199 (Venetoclax), a BH3-mimetic Bcl-2 inhibitor, does not cause CaBritish journal of pharmacology · 2019Article
- HAP1 loss confers l-asparaginase resistance in ALL by downregulating the calpain-1-Bid-caspase-3/12 pathway.Blood · 2019Article
- Trypsin-encodingHaematologica · 2019Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Exocytotic secretion of digestive enzymes from pancreatic acinar cells is elicited by physiological cytosolic Ca(2+) signals, occurring as repetitive short-lasting spikes largely confined to the secretory granule region, that stimulate mitochondrial adenosine triphosphate (ATP) production. By contrast, sustained global cytosolic Ca(2+) elevations decrease ATP levels and cause necrosis, leading to the disease acute pancreatitis (AP). Toxic Ca(2+) signals can be evoked by products of alcohol and fatty acids as well as bile acids. Here, we have investigated the mechanism by which l-asparaginase evokes AP. Asparaginase is an essential element in the successful treatment of acute lymphoblastic leukaemia, the most common type of cancer affecting children, but AP is a side-effect occurring in about 5-10% of cases. Like other pancreatitis-inducing agents, asparaginase evoked intracellular Ca(2+) release followed by Ca(2+) entry and also substantially reduced Ca(2+) extrusion because of decreased intracellular ATP levels. The toxic Ca(2+) signals caused extensive necrosis. The asparaginase-induced pathology depended on protease-activated receptor 2 and its inhibition prevented the toxic Ca(2+) signals and necrosis. We tested the effects of inhibiting the Ca(2+) release-activated Ca(2+) entry by the Ca(2+) channel inhibitor GSK-7975A. This markedly reduced asparaginase-induced Ca(2+) entry and also protected effectively against the development of necrosis.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'.
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