H. Buniatyan Institute of Biochemistry NAS RA, 0014, Yerevan, Armenia.
Neuroendocrine Relationships Lab, Orbeli Institute of Physiology NAS RA, 0028, Yerevan, Armenia.
BMC Endocr Disord. 2022 Oct 18;22(1):250. doi: 10.1186/s12902-022-01160-x.
NADPH oxidase 1 (Nox1), which is highly expressed in the colon, is thought to play a potential role in host defense as a physical and innate immune barrier against commensal or pathogenic microbes in the gastrointestinal epithelium. Diabetes can be caused by several biological factors, including insulin resistance is one of them. Alloxan is widely used to induce insulin-dependent diabetes in experimental animals. Alloxan increases the generation of reactive oxygen species as a result of metabolic reactions in the body, along with a massive increase in cytosolic calcium concentration.
Using a universal method, a superoxide radical (О)-thermostable associate between NADPH-containing lipoprotein (NLP) and NADPH oxidase (Nox)- NLP-Nox was isolated and purified from the small intestine (SI) of control (C) and alloxan-induced diabetic (AD) albino rats.
In comparison to the C indices, in AD in the SI, an increase in the specific content of NLP-Nox associate and a decrease in the stationary concentration of produced О in liquid phase (in solution) and gas phase (during blowing by oxygen of the NLP-Nox solution) were observed. The NLP-Nox of SI associate in C and AD rats produced О by an immediate mechanism, using NLP as a substrate. The phenomenon of the hiding of the optical absorption maxima of the Nox in oxidized states at pH10,5 was observed in the composition of these SI associates of the C and AD rat groups. The characteristic absorption maxima of the «hidden» Nox were observed under these conditions after reduction by potassium dithionite.
Thus, at AD, the decrease in the stationary concentration of produced О in the solution and gas phase was compensated for by an increase in the specific amount of associate. In addition, the decrease in the stationary concentration of produced О by NLP-Nox associates at AD can be linked to a decrease in the level of NADPH in NLP-Nox composition. This could be used as a new mechanism of AD pathogenesis.
NADPH 氧化酶 1(Nox1)在结肠中高度表达,被认为在宿主防御中发挥潜在作用,作为胃肠道上皮中共生或致病微生物的物理和先天免疫屏障。糖尿病可由多种生物学因素引起,其中包括胰岛素抵抗。 用于诱导实验动物胰岛素依赖性糖尿病的常用试剂是丙烯醛。丙烯醛会导致体内代谢反应产生大量活性氧(ROS),同时细胞溶质钙浓度也会大量增加。
使用通用方法,从小肠(SI)中分离并纯化来自对照(C)和丙烯醛诱导的糖尿病(AD)白化大鼠的含 NADPH 的脂蛋白(NLP)和 NADPH 氧化酶(Nox)之间的超氧自由基(O)热稳定缔合物(NLP-Nox)。
与 C 指数相比,在 AD 的 SI 中,观察到 NLP-Nox 缔合物的比含量增加,以及液相(溶液中)和气相(通过向 NLP-Nox 溶液吹氧)中产生的 O 的静态浓度降低。C 和 AD 大鼠的 NLP-Nox 缔合物通过即时机制使用 NLP 作为底物产生 O。在 pH10.5 下,观察到氧化状态下 Nox 的光吸收最大值隐藏在这些 SI 缔合物的 C 和 AD 大鼠组的组成中的现象。在这些条件下,在用连二亚硫酸钠还原后观察到“隐藏”Nox 的特征吸收最大值。
因此,在 AD 中,通过增加缔合物的比含量来补偿溶液和气相中产生的 O 的静态浓度降低。此外,AD 中 NLP-Nox 缔合物产生的 O 的静态浓度降低可能与 NLP-Nox 组成中 NADPH 水平降低有关。这可以作为 AD 发病机制的新机制。