Saha Sarama, Bornstein Stefan R, Graessler Juergen, Chakrabarti Sasanka, Kopprasch Steffi
Department of Internal Medicine III, Carl Gustav Carus Medical School, Technical University of Dresden, Dresden, Germany.
Department of Biochemistry, AIIMS, Rishikesh, India.
Horm Metab Res. 2017 Sep;49(9):716-718. doi: 10.1055/s-0043-115226. Epub 2017 Aug 23.
Increased plasma aldosterone concentration is significantly associated with dementia, which is accentuated by diabetes mellitus (DM). Angiotensin II (AngII) deteriorates cognitive function through neuronal degradation. Lipoproteins, a major source of cholesterol for aldosterone biosynthesis, undergo glycoxidative modifications in the presence of hyperglycemia. We hypothesize that there would be a pathophysiological link between diabetically-modified lipoproteins, angiotensin II, and increased plasma aldosterone concentration for induction of cognitive impairment. Glycoxidized lipoproteins produce significantly more aldosterone from AngII-sensitized adrenocortical cells compared to their native counterparts. The elucidation of signaling mechanisms revealed that modified lipoproteins follow the similar signaling mechanism like AngII for adrenocortical aldosterone release via ERK1/2 and Janus kinase-2 (Jak-2)-mediated pathways. The enhanced aldosterone release from AngII-sensitized adrenocortical cells induced by glycoxidatively modified lipoproteins may play a crucial role in cognitive dysfunction in diabetic individuals along with AngII via a prevailing mode of signaling cascade involving ERK1/2- and Jak-2-dependent pathways.
血浆醛固酮浓度升高与痴呆显著相关，糖尿病会加剧这种关联。血管紧张素II（AngII）通过神经元降解损害认知功能。脂蛋白是醛固酮生物合成的主要胆固醇来源，在高血糖情况下会发生糖氧化修饰。我们假设，糖尿病修饰的脂蛋白、血管紧张素II和血浆醛固酮浓度升高之间存在病理生理联系，可导致认知障碍。与天然脂蛋白相比，糖氧化脂蛋白从AngII致敏的肾上腺皮质细胞产生的醛固酮明显更多。信号机制的阐明表明，修饰的脂蛋白遵循与AngII类似的信号机制，通过ERK1/2和Janus激酶-2（Jak-2）介导的途径促进肾上腺皮质醛固酮释放。糖氧化修饰脂蛋白诱导AngII致敏的肾上腺皮质细胞醛固酮释放增加，可能与AngII一起，通过涉及ERK1/2和Jak-2依赖性途径的主要信号级联模式，在糖尿病个体的认知功能障碍中起关键作用。
