Modifications of calcium metabolism and apoptosis after ammonia nitrogen exposure imply a tumorous fate in clam Ruditapes philippinarum?

• Published in: Aquatic toxicology 2022-04, Vol.245, p.106110-106110, Article 106110
• Main Authors: Cong, Ming, Xu, Hongchao, Li, Yuanmei, Tian, Wenwen, Lv, Jiasen
• Format: Article
• Language: English
• Subjects: Ammonia nitrogen; Apoptosis; Bcl-2; Calcium metabolism; ROS; Tumorous fate
• ISSN: 0166-445X; 1879-1514
• DOI: 10.1016/j.aquatox.2022.106110

•Environmental concentrations of NH3N induced ROS production in clam gill cells.•NH3N exposure decreased Ca2+ concentrations and increased caspase-3 activities.•NH3N exposure increased mRNA levels of three Ca2+ exchangers and two Bcl-2 genes.•Caspase 3, Bcl2–2 and Na+/Ca2+ exchanger 3 could be used as potential biomarkers. Ammonia nitrogen (NH3N) is a kind of toxic inorganic nitrogen that has been a great ecological stressor to the marine organisms for quite a few years in Chinese coastal area. Toxic mechanism of ammonia nitrogen on marine bivalve is not well elucidated, especially in calcium metabolism and apoptosis. In the present study, clams Ruditapes philippinarum were used as the experiment animals to receive NH3N exposure with environmental concentrations for 21 days. Results showed that NH3N exposure induced ROS production, decreased Ca2+ concentration, and increased caspase 3 activities in the clam gill cells. In addition, three kinds of Ca2+ exchanger genes, e. g. Na+/K+/Ca2+ exchanger 2, Na+/Ca2+ exchanger 3 and monovalent cation/H+ antiporter, exhibited significant increments in transcription to eliminate intracellular Ca2+. Besides, NH3N exposure significantly increased mRNA expression levels of key anti-apoptotic regulator Bcl-2 genes (Bcl2–1 and Bcl2–1), which would inhibit the apoptosis degree in gill cells. Taken together, increased Ca2+-extrusion and apoptosis inhibition would act cooperatively to alleviate the apoptosis degree and extend the lifespan, so that some kind of tumor might develop in oxidative damaged gill cells after NH3N exposure. Therefore, it is predicted that NH3N exposure will probably bring the clam R. philippinarum a tumorous fate, which will be a great challenge for the healthy development of molluscs aquaculture under the current pollution condition. In addition, caspase 3 activity and mRNA expression levels of Bcl2–2 and Na+/Ca2+ exchanger 3 could be used as potential clam biomarkers to indicate NH3N pollution.