当前位置: X-MOL 学术Toxicol. In Vitro › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Effects of environmental metals on mitochondrial bioenergetics of the CD-1 mice pancreatic beta-cells
Toxicology in Vitro ( IF 3.2 ) Pub Date : 2020-10-08 , DOI: 10.1016/j.tiv.2020.105015
Ekramy Elmorsy 1 , Ayat Al-Ghafari 2 , Huda Al Doghaither 3 , Jihan Ghulam 4
Affiliation  

Environmental metals are believed to have diabetogenic effects without any clear underlying mechanisms. The study investigated the effects of metals, lead (Pb), mercury (Hg), cadmium (Cd), and molybdenum (Mo), on the bioenergetics of isolated pancreatic β-cells from CD-1 mice via different functional and structural techniques. The tested metals caused significant decrease in ATP production in concentration and exposure duration-dependent pattern; Cd was the most potent cytotoxic metal. In ATP assay estimated effective concentration 50 (EC50) (25, 40, 20, and 100 μM for Pb, Hg, Cd, and Mo, respectively), the metals also significantly inhibited the glucose-stimulated insulin secretion (GSIS), mitochondrial complexes activity, mitochondrial membranes potential, and oxygen consumption rates of the treated cells with parallel increases in their lactate production and in the mitochondrial swelling and permeation of their inner mitochondrial membranes to potassium (K+) and hydrogen (H+) ions. In addition, Cd, Pb, and Hg produced significant increases in mitochondrial membrane fluidity (MMF) with significant decreases in saturated/unsaturated fatty acid ratios. In 10 μM concentration, away from Mo, the three metals showed inhibitory effects on the mitochondrial functions to variable degrees. Only Cd showed significant effect on MMF and fatty acid ratios at a concentration of 10 μM. In conclusion, the tested metals significantly affected the bioenergetics of the pancreatic β-cells with significant effect on GSIS. Cd showed the most significant functional and structural effects on their mitochondria followed by Pb, then Hg, while Mo was almost safe up to 10 μM concentration. Hence, bioenergetic mitochondrial disruption can be considered as an underlying mechanism of the diabetogenic effects of the tested metals.



中文翻译:

环境金属对CD-1小鼠胰腺β细胞线粒体生物能学的影响

环境金属被认为具有致糖尿病作用,但没有任何明确的潜在机制。该研究通过不同的功能和结构技术研究了金属、铅 (Pb)、汞 (Hg)、镉 (Cd) 和钼 (Mo) 对来自 CD-1 小鼠的分离胰腺 β 细胞的生物能学的影响。测试的金属在浓度和暴露时间依赖性模式中导致 ATP 产量显着下降;Cd 是最有效的细胞毒性金属。在 ATP 测定中估计的有效浓度 50 (EC50)(Pb、Hg、Cd 和 Mo 分别为 25、40、20 和 100 μM),金属还显着抑制了葡萄糖刺激的胰岛素分泌 (GSIS)、线粒体复合物活性,线粒体膜电位,+ ) 和氢 (H +) 离子。此外,Cd、Pb 和 Hg 使线粒体膜流动性 (MMF) 显着增加,饱和/不饱和脂肪酸比率显着降低。在 10 μM 浓度下,远离 Mo,三种金属对线粒体功能表现出不同程度的抑制作用。只有 Cd 在 10 μM 的浓度下对 MMF 和脂肪酸比率显示出显着影响。总之,所测试的金属显着影响胰腺 β 细胞的生物能量学,对 GSIS 有显着影响。Cd 对其线粒体显示出最显着的功能和结构影响,其次是 Pb,然后是 Hg,而 Mo 在高达 10 μM 的浓度下几乎是安全的。因此,生物能线粒体破坏可以被认为是所测试金属致糖尿病作用的潜在机制。

更新日期:2020-10-30
down
wechat
bug