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Pathogenesis of Alzheimer’s disease (AD), which is characterised by accumulation of extracellular deposits of β-amyloid peptide
(Aβ) in the brain, has recently been linked to vascular disorders such as ischemia and stroke. Aβ is constantly produced in
the brain from amyloid precursor protein (APP) through its cleavage by β- and γ-secretases and certain Aβ species are toxic
for neurones. The brain has an endogenous mechanism of Aβ removal via proteolytic degradation and the zinc metalloproteinase
neprilysin (NEP) is a critical regulator of Aβ concentration. Down-regulation of NEP could predispose to AD. By comparing
the effects of hypoxia and oxidative stress on expression and activity of the Aβ-degrading enzyme NEP in human neuroblastoma
NB7 cells and rat primary cortical neurones we have demonstrated that hypoxia reduced NEP expression at the protein and mRNA
levels as well as its activity. On contrary in astrocytes hypoxia increased NEP mRNA expression.
Special issue dedicated to Dr. Moussa Youdim. 相似文献
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Xiaojing Liu Heng Du Dan Chen Hai Yuan Wenbin Chen Wenyu Jia Xiaolei Wang Xia Li Ling Gao 《Biochemical and biophysical research communications》2019,508(4):1202-1208
Introduction
Inflammation and oxidative stress are closely correlated in the pathology of cardiovascular disease. Mitochondrial cyclophilin D (CypD), the important modulator for mPTP opening, is increasingly recognized as a key regulator of cellular ROS generation. Besides, its association with cell inflammation is also being discovered. However, the effects of CypD in modulating vascular inflammatory response is unknown. We sought to investigate whether CypD deficiency attenutes vascular inflammation under physical conditions.Methods and results
We adopted CypD KO mouse and their littermate controls to observe the effects of CypD deficiency on aortic mitochondrial functions and vascular inflammation. As we found in our study, we confirmed that under physical conditions, CypD deficiency enhanced mouse whole body metabolic status, increased aortic mitochondrial complex III activity and decreased mitochondrial ROS generation. Functionally, CypD deficiency also attenuated inflammatory molecules expression, including VCAM-1, IL-6 and TNF-α in mouse aorta.Conclusions
Our results review that mitochondrial CypD is involved in the regulation of inflammation in aorta and provide insights that blocking mitochondrial CypD enhances vascular resistance to inflammatory injuries. 相似文献4.
Kungsadal Sirijariyawat Atcharaporn Ontawong Siripong Palee Savitree Thummasorn Chayodom Maneechote Oranit Boonphang Varanuj Chatsudthipong Nipon Chattipakorn Chutima Srimaroeng 《生物化学与生物物理学报:疾病的分子基础》2019,1865(9):2342-2355
Acute kidney injury (AKI) is a high frequent and common complication following acute myocardial infarction (AMI). This study examined and identified the effect of AMI-induced AKI on organic anion transporter 1 (Oat1) and Oat3 transport using clinical setting of pre-renal AKI in vivo. Cardiac ischaemia (CI) and cardiac ischaemia and reperfusion (CIR) were induced in rats by 30-min left anterior descending coronary artery occlusion and 30-min occlusion followed by 120-min reperfusion, respectively. Renal hemodynamic parameters, mitochondrial function and Oat1/Oat3 expression and function were determined along with biochemical markers. Results showed that CI markedly reduced renal blood flow and pressure by approximately 40%, while these parameters were recovered during reperfusion. CI and CIR progressively attenuated renal function and induced oxidative stress by increasing plasma BUN, creatinine and malondialdehyde levels. Correspondingly, SOD, GPx, CAT mRNAs were decreased, while TNFα, IL1β, COX2, iNOS, NOX2, NOX4, and xanthine oxidase were increased. Mitochondrial dysfunction as indicated by increasing ROS, membrane depolarisation, swelling and caspase3 activation were shown. Early significant detection of AKI; KIM1, IL18, was found. All of which deteriorated para-aminohippurate transport by down-regulating Oat1 during sudden ischaemia. This consequent blunted the trafficking rate of Oat1/Oat3 transport via down-regulating PKCζ/Akt and up-regulating PKCα/NFκB during CI and CIR. Thus, this promising study indicates that CI and CIR abruptly impaired renal Oat1 and regulatory proteins of Oat1/Oat3, which supports dysregulation of remote sensing and signalling and inter-organ/organismal communication. Oat1, therefore, could potentially worsen AKI and might be a potential therapeutic target for early reversal of such injury. 相似文献
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The hallmarks of tumor tissue are not only genetic aberrations but also the presence of metabolic and oxidative stress as a result of hypoxia and lactic acidosis. The stress activates several prosurvival pathways including metabolic remodeling, autophagy, antioxidant response, mitohormesis, and glutaminolysis, whose upregulation in tumors is associated with a poor survival of patients, while their activation in healthy tissue with statins, metformin, physical activity, and natural compounds prevents carcinogenesis. This review emphasizes the dual role of stress response pathways in cancer and suggests the integrative understanding as a basis for the development of rational therapy targeting the stress response. 相似文献