钒(V)是动物体内必需的矿物元素,但是过量的V会导致许多疾病,影响人类和动物的健康。然而,V暴露下线粒体相关内质网膜(MAMs)与炎症之间的分子串扰仍处于探索阶段。进行这项研究是为了确定鸭子在V暴露下MAM与炎症之间的分子串扰。在这项研究中,鸭肝细胞用NaVO3(0μM,100μM,和200μM)和2-氨基乙基二苯基硼酸酯(2-APB)(IP3R抑制剂)单独或联合使用24小时。数据显示,V暴露诱导的细胞液泡化,细胞间隙增大,密度和生存力降低。同时,过氧化氢(H2O2),丙二醛(MDA),过氧化氢酶(CAT),超氧化物歧化酶(SOD),在V处理下,活性氧(ROS)水平上调。此外,过量的V可能导致MAMs结构的显著减少,膜结构的破坏和细胞内Ca2和线粒体Ca2的过载。此外,V治疗导致MAMs相关因子水平显著上调(IP3R,Mfn2,Grp75,MCU,VDAC1),但下调IL-18,IL-1β的水平,和细胞上清液中的乳酸脱氢酶(LDH)。此外,它还显着升高了炎症相关因子的水平(NLRP3,ASC,caspase-1,MAVS,IL-18,IL-1β,和TXNIP)。然而,IP3R表达的抑制减弱了V诱导的上述指标的变化。总的来说,我们的结果表明,钙稳态的维持可以通过MAMs保护鸭肝细胞免受V引起的炎症损伤。
Vanadium (V) is an essential mineral element in animals, but excessive V can lead to many diseases, affecting the health of humans and animals. However, the molecular crosstalk between mitochondria-associated endoplasmic reticulum membranes (MAMs) and inflammation under V exposure is still at the exploratory stage. This study was conducted to determine the molecular crosstalk between MAMs and inflammation under V exposure in ducks. In this study, duck hepatocytes were treated with NaVO3 (0 μM, 100 μM, and 200 μM) and 2-aminoethyl diphenyl borate (2-APB) (IP3R inhibitor) alone or in combination for 24 h. The data showed that V exposure-induced cell vacuolization, enlarged intercellular space, and decreased density and viability. Meanwhile, hydrogen peroxide (H2O2), malonaldehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and reactive oxygen species (ROS) levels were upregulated under V treatment. In addition, excessive V could lead to a marked reduction in the MAMs structure, destruction of the membrane structure and overload of intracellular Ca2+ and mitochondrial Ca2+. Moreover, V treatment resulted in notable upregulation of the levels of MAMs-relevant factors (IP3R, Mfn2, Grp75, MCU, VDAC1) but downregulated the levels of IL-18, IL-1β, and lactate dehydrogenase (LDH) in the cell supernatant. Additionally, it also significantly elevated the levels of inflammation-relevant factors (NLRP3, ASC, caspase-1, MAVS, IL-18, IL-1β, and TXNIP). However, the inhibition of IP3R expression attenuated the V-induced variations in the above indicators. Collectively, our results revealed that the maintenance of calcium homeostasis could protect duck hepatocytes from V-induced inflammation injury via MAMs.