Enhanced activity of superoxide dismutase is a common response to dietary and genetically induced increased cholesterol levels

Dominko, Kristina; Đikić, Domagoj; Hečimović, Silva

doi:10.1080/1028415x.2018.1511027

Cited by 6 publications

(13 citation statements)

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“…In NPC1 patient-derived fibroblasts, downregulation of the gene expression and a diminished protein level of the SOD2 were also found [ 26 , 27 ]. However, Dominko and colleagues [ 22 ] found changes neither of the SOD1 nor the SOD2 protein level in NPC1-deficient CHO cells, although they detected changes in SOD activity [ 22 ]. Unexpectedly, we did not observe any alterations in the regulation or expression of SOD1 and SOD2.…”

Section: Discussionmentioning

confidence: 99%

“…Similar hallmarks of OS can be detected in different in vitro models. In NPC-deficient neuroblastoma cells, higher ROS levels were detected by flow cytometry measurements [ 13 , 22 ]. Dominko and colleagues [ 22 ] pointed out differences in the defense system of the NPC1-deficient CHO cells represented by lower GSH content, decreased catalase activity and elevated SOD activity.…”

Section: Introductionmentioning

confidence: 99%

“…In NPC-deficient neuroblastoma cells, higher ROS levels were detected by flow cytometry measurements [ 13 , 22 ]. Dominko and colleagues [ 22 ] pointed out differences in the defense system of the NPC1-deficient CHO cells represented by lower GSH content, decreased catalase activity and elevated SOD activity. Similarly, SOD alterations, as well as differences in the glutathione transferase (GST), were found in the cerebrospinal fluid of NPC1 patients [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

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Oxidative Stress and Alterations in the Antioxidative Defense System in Neuronal Cells Derived from NPC1 Patient-Specific Induced Pluripotent Stem Cells

Jürs

Völkner

Liedtke

et al. 2020

IJMS

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Oxidative stress (OS) represents a state of an imbalanced amount of reactive oxygen species (ROS) and/or a hampered efficacy of the antioxidative defense system. Cells of the central nervous system are particularly sensitive to OS, as they have a massive need of oxygen to maintain proper function. Consequently, OS represents a common pathophysiological hallmark of neurodegenerative diseases and is discussed to contribute to the neurodegeneration observed amongst others in Alzheimer’s disease and Parkinson’s disease. In this context, accumulating evidence suggests that OS is involved in the pathophysiology of Niemann-Pick type C1 disease (NPC1). NPC1, a rare hereditary neurodegenerative disease, belongs to the family of lysosomal storage disorders. A major hallmark of the disease is the accumulation of cholesterol and other glycosphingolipids in lysosomes. Several studies describe OS both in murine in vivo and in vitro NPC1 models. However, studies based on human cells are limited to NPC1 patient-derived fibroblasts. Thus, we analyzed OS in a human neuronal model based on NPC1 patient-specific induced pluripotent stem cells (iPSCs). Higher ROS levels, as determined by DCF (dichlorodihydrofluorescein) fluorescence, indicated oxidative stress in all NPC1-deficient cell lines. This finding was further supported by reduced superoxide dismutase (SOD) activity. The analysis of mRNA and protein levels of SOD1 and SOD2 did not reveal any difference between control cells and NPC1-deficient cells. Interestingly, we observed a striking decrease in catalase mRNA and protein levels in all NPC1-deficient cell lines. As catalase is a key enzyme of the cellular antioxidative defense system, we concluded that the lack of catalase contributes to the elevated ROS levels observed in NPC1-deficient cells. Thus, a restitution of a physiological catalase level may pose an intervention strategy to rescue NPC1-deficient cells from the repercussions of oxidative stress contributing to the neurodegeneration observed in NPC1.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Oxidative Stress and Alterations in the Antioxidative Defense System in Neuronal Cells Derived from NPC1 Patient-Specific Induced Pluripotent Stem Cells

Jürs

Völkner

Liedtke

et al. 2020

IJMS

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“…Interestingly, we noticed a significant and positive correlation between SOD and cholesterol, HDL-C and LDL-C in PD patients. It has been shown that increased cholesterol, either in vivo in cholesterol-fed wt mice or in vitro in genetically induced cholesterol accumulation due to NPC1 loss-of-function, could potentiate SOD activity, suggesting that SOD might be a prime target and the first defense mechanism of oxidative stress response upon increased cholesterol (Dominko et al, 2018). Multiple lines of evidence already indicate that a high level of LDL-C could cause the free radical formation and excessive oxidative stress, which initially leads to a progressive increase in endogenous enzymatic scavengers like SOD (Gupta et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, SOD mimetic has been successfully used to prevent the extent of inflammation (De Lazzari et al, 2018;Ren et al, 2018). As mentioned above, SOD is the prime target and the first defense mechanism of oxidative stress response upon increased cholesterol /LDL-C (Gupta et al, 2009;Dominko et al, 2018), which may prevent the inflammatory response caused by cholesterol /LDL-C to some extent. Therefore, there seems to be a strong and complicated interaction between hsCRP/cholesterol/LDL-C pro-inflammatory function and SOD anti-inflammatory function, which may influence the cognitive dysfunctions in PD patients.…”

Section: Discussionmentioning

confidence: 99%

Contra-Directional Expression of Plasma Superoxide Dismutase with Lipoprotein Cholesterol and High-Sensitivity C-reactive Protein as Important Markers of Parkinson’s Disease Severity

Yang

Chang

Que

et al. 2020

Front. Aging Neurosci.

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Aim: Oxidative stress and inflammation play critical roles in the neuropathogenesis of PD. We aimed to evaluate oxidative stress and inflammation status by measuring serum superoxide dismutase (SOD) with lipoprotein cholesterol and high-sensitivity C-reactive protein (hsCRP) respectively in PD patients, and explore their correlation with the disease severity. Methods: We performed a cross-sectional study that included 204 PD patients and 204 age-matched healthy controls (HCs). Plasma levels of SOD, hsCRP, total cholesterol, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured. A series of neuropsychological assessments were performed to rate the severity of PD. Results: The plasma levels of SOD (135.7 ± 20.14 vs. 147.2 ± 24.34, P < 0.0001), total cholesterol, HDL-C and LDL-C in PD were significantly lower than those in HCs; the hsCRP level was remarkably increased in PD compared to HC (2.766 ± 3.242 vs. 1.637 ± 1.597, P < 0.0001). The plasma SOD was negatively correlated with the hsCRP, while positively correlated with total cholesterol, HDL-C, and LDL-C in PD patients. The plasma SOD were negatively correlated with H&Y, total UPDRS, UPDRS (I), UPDRS (II), and UPDRS (III) scores, but positively correlated with MoCA and MMSE scores. Besides,

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Lipid metabolism and oxidative stress in patients with Alzheimer's disease and amnestic mild cognitive impairment

Nie,

Chu,

Qin

et al. 2023

Brain Pathology

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Lipid metabolism and oxidative stress are key mechanisms in Alzheimer's disease (AD). The link between plasma lipid metabolites and oxidative stress in AD patients is poorly understood. This study was to identify markers that distinguish AD and amnestic mild cognitive impairment (aMCI) from NC, and to reveal potential links between lipid metabolites and oxidative stress. We performed non‐targeted lipid metabolism analysis of plasma from patients with AD, aMCI, and NC using LC–MS/MS. The plasma malondialdehyde (MDA), glutathione peroxidase (GSH‐Px), and superoxide dismutase (SOD) levels were assessed. We found significant differences in lipid metabolism between patients with AD and aMCI compared to those in NC. AD severity is associated with lipid metabolites, especially TG (18:0_16:0_18:0) + NH4, TG (18:0_16:0_16:0) + NH4, LPC(16:1e)‐CH3, and PE (20:0_20:4)‐H. SPH (d16:0) + H, SPH (d18:1) + H, and SPH (d18:0) + H were high‐performance markers to distinguish AD and aMCI from NC. The AUC of three SPHs combined to predict AD was 0.990, with specificity and sensitivity as 0.949 and 1, respectively; the AUC of three SPHs combined to predict aMCI was 0.934, with specificity and sensitivity as 0.900, 0.981, respectively. Plasma MDA concentrations were higher in the AD group than in the NC group (p = 0.003), whereas plasma SOD levels were lower in the AD (p < 0.001) and aMCI (p = 0.045) groups than in NC, and GSH‐Px activity were higher in the AD group than in the aMCI group (p = 0.007). In addition, lipid metabolites and oxidative stress are widely associated. In conclusion, this study distinguished serum lipid metabolism in AD, aMCI, and NC subjects, highlighting that the three SPHs can distinguish AD and aMCI from NC. Additionally, AD patients showed elevated oxidative stress, and there are complex interactions between lipid metabolites and oxidative stress.

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Enhanced activity of superoxide dismutase is a common response to dietary and genetically induced increased cholesterol levels

Cited by 6 publications

References 67 publications

Oxidative Stress and Alterations in the Antioxidative Defense System in Neuronal Cells Derived from NPC1 Patient-Specific Induced Pluripotent Stem Cells

Oxidative Stress and Alterations in the Antioxidative Defense System in Neuronal Cells Derived from NPC1 Patient-Specific Induced Pluripotent Stem Cells

Contra-Directional Expression of Plasma Superoxide Dismutase with Lipoprotein Cholesterol and High-Sensitivity C-reactive Protein as Important Markers of Parkinson’s Disease Severity

Lipid metabolism and oxidative stress in patients with Alzheimer's disease and amnestic mild cognitive impairment

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