Pyridine nucleotide regulation of hepatic endoplasmic reticulum calcium uptake. Issue 12 (20th June 2019) - Wang, Xudong
Abstract: Pyridine nucleotides serve an array of intracellular metabolic functions such as, to name a few, shuttling electrons in enzymatic reactions, safeguarding the redox state against reactive oxygen species, cytochrome P450 (CYP) enzyme detoxification pathways and, relevant to this study, the regulation of ion fluxes. In particular, the maintenance of a steep calcium gradient between the cytosol and endoplasmic reticulum (ER), without which apoptosis ensues, is achieved by an elaborate combination of energy–requiring ER membrane pumps and efflux channels. In liver microsomes, net calcium uptake was inhibited by physiological concentrations of NADP. In the presence of 1 mmol/L NADP, calcium uptake was attenuated by nearly 80%, additionally, this inhibitory effect was blunted by concomitant addition of NADPH. No other nicotinamide containing compounds ‐save a slight inhibition by NAADP‐hindered calcium uptake; thus, only oxidized pyridine nucleotides, or related compounds with a phosphate moiety, had an imposing effect. Moreover, the NADP inhibition was evident even after selectively blocking ER calcium efflux channels. Given the fundamental role of endoplasmic calcium homeostasis, it is plausible that changes in cytosolic NADP concentration, for example, during anabolic processes, could regulate net ER calcium uptake. Abstract : NADP inhibits calcium uptake in hepatic microsomes and the site of action involves the ingress component of net calcium uptake. Given the fundamental role of endoplasmic calcium homeostasis, it is plausible that changes in cytosolic NADP concentration, for example, during anabolic processes, could regulate net endoplasmic reticulum calcium uptake.