Oxidative and carbonyl stress as a factors of the modification of proteins and DNA destruction in diabetes

Ланкин, В. З.; Tikhaze, A. K.; Konovalova, G. G.; Odinokova, O A; Doroshchuk, N. A.; Чазова, И Е

doi:10.26442/terarkh2018901046-50

Cited by 5 publications

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“…The accumulation of glyoxal and methylglyoxal in the plasma of diabetic patients has been repeatedly confirmed [ 38 , 39 , 40 ]. At the same time, the presence of oxidative stress in diabetes is evidenced by a decrease in telomere length of nuclear blood cells [ 45 ], as well as an increase in the level of 8-hydroxy-2-deoxyguanosine, the end product of oxidative DNA destruction, in the blood and urine of type 2 diabetic patients [ 45 ]. It should be noted that 8-hydroxy-2-deoxyguanosine is a recognized biomarker of oxidative stress [ 46 ] and its accumulation is not associated with the development of carbonyl stress.…”

Section: Carbonyl Stress In Diabetes and The Role Of Modified Ldl In ...mentioning

confidence: 99%

“…Just as in atherosclerosis, in patients with type 2 diabetes there is an increase in the carbonyl modification of LDL [ 45 ] and a sharp decrease in the activity of erythrocyte Cu,Zn-SOD and GSH-Px [ 45 , 47 ], which is a reflection of carbonyl stress. A significant increase in glyoxal and methylglyoxal levels in the blood of type 2 diabetic patients [ 38 , 39 , 40 ] can cause modification of LDL, which is detected by scavenger receptor macrophages and, thus, can induce the accumulation of LDL in the vascular wall with the subsequent development of lipoid lesions [ 38 ].…”

Section: Carbonyl Stress In Diabetes and The Role Of Modified Ldl In ...mentioning

confidence: 99%

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Dicarbonyl-Dependent Modification of LDL as a Key Factor of Endothelial Dysfunction and Atherosclerotic Vascular Wall Damage

2022

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The review presents evidence that the main damage to the vascular wall occurs not from the action of “oxidized” LDL, which contain hydroperoxy acyls in the phospholipids located in their outer layer, but from the action of LDL particles whose apoprotein B-100 is chemically modified with low molecular weight dicarbonyls, such as malondialdehyde, glyoxal, and methylglyoxal. It has been argued that dicarbonyl-modified LDL, which have the highest cholesterol content, are particularly “atherogenic”. High levels of dicarbonyl-modified LDL have been found to be characteristic of some mutations of apoprotein B-100. Based on the reviewed data, we hypothesized a common molecular mechanism underlying vascular wall damage in atherosclerosis and diabetes mellitus. The important role of oxidatively modified LDL in endothelial dysfunction is discussed in detail. In particular, the role of the interaction of the endothelial receptor LOX-1 with oxidatively modified LDL, which leads to the expression of NADPH oxidase, which in turn generates superoxide anion radical, is discussed. Such hyperproduction of ROS can cause destruction of the glycocalyx, a protective layer of endotheliocytes, and stimulation of apoptosis in these cells. On the whole, the accumulated evidence suggests that carbonyl modification of apoprotein B-100 of LDL is a key factor responsible for vascular wall damage leading to atherogenesis and endothelial dysfunction. Possible ways of pharmacological correction of free radical processes in atherogenesis and diabetogenesis are also discussed.

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Section: Carbonyl Stress In Diabetes and The Role Of Modified Ldl In ...mentioning

confidence: 99%

Section: Carbonyl Stress In Diabetes and The Role Of Modified Ldl In ...mentioning

confidence: 99%

Dicarbonyl-Dependent Modification of LDL as a Key Factor of Endothelial Dysfunction and Atherosclerotic Vascular Wall Damage

2022

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“…Our study obtained data on lower values of TBARs in the studied groups. In contrast, a number of studies have shown an increase in the values of lipid peroxidation end products in DN [20,23,56]. Pestana et al, however, found no significant differences when studying this parameter [57].…”

Section: Discussionmentioning

confidence: 91%

“…MGO is considered to be an important biomarker for complications of diabetes because of its close association with the glycation processes, β-cell dysfunction, and insulin resistance [52]. MGO covalently modifies DNA, RNA, and protein, forming advanced glycation end products (AGEPS) [23,58]. AGEPS accumulate, decompose slowly, and persist for a long time in the vascular bed, even after euglycemia is reached, which has been dubbed the "metabolic memory" mechanism [59].…”

Section: Discussionmentioning

confidence: 99%

“…The interaction of ROS with cellular components-lipids, proteins, and DNA-ultimately results in modification of their structure, and these modifications can persist in DM patients for a prolonged period, even after achieving normoglycemia [21][22][23][24][25]. This phenomenon underlies the so-called "metabolic memory" mechanism that is based upon the products of oxidative damage [22,26].…”

Section: Introductionmentioning

confidence: 99%

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Receiver Operator Characteristic (ROC) Analysis of Lipids, Proteins, DNA Oxidative Damage, and Antioxidant Defense in Plasma and Erythrocytes of Young Reproductive-Age Men with Early Stages of Type 1 Diabetes Mellitus (T1DM) Nephropathy in the Irkutsk Region, Russia

et al. 2022

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Oxidative stress plays a leading role in the pathogenesis of diabetic nephropathy. However, many aspects of oxidative stress reactions in the initial stages of this disease are not fully understood. The men cohort is of particular interest because of the severe effects of diabetes on their urogenital system. The aim of this study is to assess the intensity of lipids, proteins, DNA oxidative damage, blood antioxidant defense enzymatic, and activity of non-enzymatic components in men with type 1 diabetes mellitus (T1DM) in the early stages of diabetic nephropathy using receiver operator characteristic (ROC) analysis. This study included eighty-nine reproductive-age men in the initial stages of diabetic nephropathy (DN) and thirty-nine age- and sex-matched individuals not suffering from glycemic disorders. The DN patients were divided into two subgroups: stage 1 patients (urinary albumin < 30 mg/day and albumin/creatinine ratio < 3 mg/mmol (n = 45)) and stage 2 patients (urinary albumin 30–300 mg/day and albumin/creatinine ratio 3–30 mg/mmol (n = 44)). Levels of oxidative damage products (conjugated dienes (CDs), thiobarbituric acid reactants (TBARs), methylglyoxal (MGO), and 8-hydroxy-2’-deoxyguanosine (8-OHdG)) and antioxidants (glutathione peroxidase (GPx), glutathione S-transferases π (GSTp), glutathione reductase (GR), copper and zinc-containing superoxide dismutase 1 (SOD-1), total antioxidant status (TAS), α-tocopherol, retinol, reduced glutathione (GSH), and oxidative glutathione (GSSG)) were estimated in plasma and erythrocytes. Oxidative damage to cellular structures (higher values of median CDs (1.68 µmol/L; p = 0.003), MGO (3.38 mg/L; p < 0.001) in the stage 1 group and CDs (2.28 µmol/L; p < 0.0001), MGO (3.52 mg/L; p < 0.001), 8-OHdG (19.44 ng/mL; p = 0.010) in the stage 2 group) and changes in the antioxidant defense system (lower values of TAS (1.14 units; p = 0.011), α-tocopherol (12.17 µmol/L; p = 0.009), GPx (1099 units; p = 0.0003) and elevated levels of retinol (1.35 µmol/L; p < 0.001) in the group with stage 1; lower values of α-tocopherol (12.65 µmol/L; p = 0.033), GPx (1029.7 units; p = 0.0001) and increased levels of GR (292.75 units; p < 0.001), GSH (2.54 mmol/L; p = 0.010), GSSG (2.31 mmol/L; p < 0.0001), and retinol (0.81 µmol/L; p = 0.005) in the stage 2 group) were identified. The ROC analysis established that the following indicators have the highest diagnostic significance for stage 1 diabetic nephropathy: CDs (AUC 0.755; p < 0.0001), TBARs (AUC 0.748; p = 0.0001), MGO (AUC 0.720; p = 0.0033), retinol (AUC 0.932; p < 0.0001), GPx (AUC 0.741; p = 0.0004), α-tocopherol (AUC 0.683; p = 0.0071), and TAS (AUC 0.686; p = 0.0052) and the following for stage 2 diabetic nephropathy: CDs (AUC 0.714; p = 0.001), TBARs (AUC 0.708; p = 0.001), 8-OHdG (AUC 0.658; p = 0.0232), GSSG (AUC 0.714; p = 0.001), and GSH (AUC 0.667; p = 0.0108). We conclude that changes in indicators of damage to lipids, proteins, DNA, and the insufficiency of antioxidant defense factors already manifest in the first stage of diabetic nephropathy in men with T1DM. The ROC established which parameters have the greatest diagnostic significance for stages 1 and 2 of diabetic nephropathy, which may be utilized as additional criteria for defining men with T1DM as being in the risk group for the development of initial manifestations of the disease and thus allow for substantiating appropriate approaches to optimize preventive measures.

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Content of Carbonyl Compounds and Parameters of Glutathione Metabolism in Men with Type 1 Diabetes Mellitus at Preclinical Stages of Diabetic Nephropathy

et al. 2021

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The content of carbonyl compounds (methylglyoxal and TBA-reactive substances) and components of the glutathione system (activities of glutathione-dependent enzymes, content of oxidized and reduced glutathione) and their interrelationships were studied in men of young reproductive age with type 1 diabetes mellitus at the stages of normo-and microalbuminuria. In patients with normoalbuminuria, the level of methylglyoxal, reduced and oxidized glutathione, and glutathione reductase activity were increased and the content of TBA-reactive substances was decreased. In the group with microalbuminuria, an increase in content of methylglyoxal and activity of glutathione-dependent enzymes relative to the control values were observed; the content of TBA-reactive substances was increased and glutathione reductase activity was decreased relative to the group with normoalbuminuria. In patients with microalbuminuria, a strong correlation between the mean glomerular filtration rate and the blood level of methylglyoxal was revealed.

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Oxidative and carbonyl stress as a factors of the modification of proteins and DNA destruction in diabetes

Cited by 5 publications

References 0 publications

Dicarbonyl-Dependent Modification of LDL as a Key Factor of Endothelial Dysfunction and Atherosclerotic Vascular Wall Damage

Dicarbonyl-Dependent Modification of LDL as a Key Factor of Endothelial Dysfunction and Atherosclerotic Vascular Wall Damage

Receiver Operator Characteristic (ROC) Analysis of Lipids, Proteins, DNA Oxidative Damage, and Antioxidant Defense in Plasma and Erythrocytes of Young Reproductive-Age Men with Early Stages of Type 1 Diabetes Mellitus (T1DM) Nephropathy in the Irkutsk Region, Russia

Content of Carbonyl Compounds and Parameters of Glutathione Metabolism in Men with Type 1 Diabetes Mellitus at Preclinical Stages of Diabetic Nephropathy

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