Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Comenius University, Sasinkova 2, 811 08, Bratislava, Slovakia.
Institute of Animal Biochemistry and Genetics, Slovak Academy of Sciences, Moyzesova 61, 900 28, Ivanka pri Dunaji, Slovakia.
Mol Cell Biochem. 2017 Nov;435(1-2):109-131. doi: 10.1007/s11010-017-3061-6. Epub 2017 May 19.
Diabetic encephalopathy, a proven complication of diabetes is associated with gradually developing end-organ damage in the CNS increasing the risk of stroke, cognitive dysfunction or Alzheimer's disease. This study investigated the response of rat cortical mitochondria to streptozotocin-induced diabetes and the potential for fish oil emulsion (FOE) to modulate mitochondrial function. Diabetes-induced deregulation of the respiratory chain function as a result of diminished complex I activity (CI) and cytochrome c oxidase hyperactivity was associated with attenuation of antioxidant defense of isolated cortical mitochondria, monitored by SOD activity, the thiol content, the dityrosine and protein-lipid peroxidation adduct formation. A parallel reduction in phosphorylation of the energy marker AMPK has pointed out to disrupted energy homeostasis. Dietary FOE administration partially preserved CI activity, restored AMPK phosphorylation, but was unable to attenuate oxidative stress and prevent the shift toward saturated fatty acids in the cardiolipin composition. Moreover, diabetes has induced alterations in the protein expression of the regulatory COX4 subunit of cytochrome c oxidase, in the inhibitory factor IF1 and ATP5A subunit of FF-ATP synthase, in the uncoupling protein UCP4 and supramolecular organization of the respiratory complexes. FOE administration to diabetic rats has partially reversed these alterations. This study suggests diabetes-induced dysfunction of brain cortical mitochondria and its modulation by FOE administration. The intricate diabetic milieu and the n-3 FA nutrigenomic strength, however require further investigations to be able to unequivocally evaluate neuroprotective and adverse effects of FOE supplementation on the diabetic brain function.
糖尿病性脑病是糖尿病的一种已知并发症，与中枢神经系统（CNS）逐渐发生的终末器官损伤有关，增加了中风、认知功能障碍或阿尔茨海默病的风险。本研究调查了链脲佐菌素（STZ）诱导的糖尿病对大鼠皮质线粒体的反应，以及鱼油乳剂（FOE）调节线粒体功能的潜力。糖尿病导致呼吸链功能失调，复合物 I（CI）活性降低和细胞色素 c 氧化酶活性亢进，与分离的皮质线粒体抗氧化防御功能减弱有关，通过 SOD 活性、巯基含量、二酪氨酸和蛋白-脂质过氧化加合物形成来监测。能量标志物 AMPK 的磷酸化减弱表明能量平衡受到干扰。饮食 FOE 给药部分保留了 CI 活性，恢复了 AMPK 磷酸化，但未能减轻氧化应激，防止心磷脂组成中饱和脂肪酸的转移。此外，糖尿病诱导了细胞色素 c 氧化酶的调节 COX4 亚基、抑制因子 IF1 和 FF-ATP 合酶的 ATP5A 亚基、解偶联蛋白 UCP4 的蛋白表达以及呼吸复合物的超分子组织发生改变。FOE 给药给糖尿病大鼠部分逆转了这些改变。本研究表明，糖尿病诱导的大脑皮质线粒体功能障碍及其被 FOE 给药的调节。然而，复杂的糖尿病环境和 n-3 FA 营养基因组强度需要进一步研究，以便能够明确评估 FOE 补充对糖尿病大脑功能的神经保护和不良反应。
