Patients with Gaucher disease display systemic oxidative stress dependent on therapy status

Although the original data on systemic oxidative stress in COVID-19 patients have recently started to emerge, we are still far from a complete profile of changes in patients’ redox homeostasis. We aimed to assess the extent of oxidative damage of proteins, lipids and DNA during the course of acute disease, as well as their association with CT pulmonary patterns. In order to obtain more insight into the origin of the systemic oxidative stress, the observed parameters were correlated with inflammatory biomarkers and biomarkers of multiorgan impairment. In this prospective study, we included 58 patients admitted between July and October 2020 with COVID-19 pneumonia. Significant changes in malondialdehyde, 8-hydroxy-2’-deoxyguanosine and advanced oxidation protein products levels exist during the course of COVID-19. Special emphasis should be placed on the fact that the pattern of changes differs between non-hospitalized and hospitalized individuals. Our results point to the time-dependent relation of oxidative stress parameters with inflammatory and multiorgan impairment biomarkers, as well as pulmonary patterns in COVID-19 pneumonia patients. Correlation between redox biomarkers and immunological or multiorgan impairment biomarkers, as well as pulmonary CT pattern, confirms the suggested involvement of neutrophils networks, IL-6 production, along with different organ/tissue involvement in systemic oxidative stress in COVID-19.

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IκBα targeting promotes oxidative stress-dependent cell death

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-01921-x ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Giovanna Carrà ◽

Giuseppe Ermondi ◽

Chiara Riganti ◽

Luisella Righi ◽

Giulia Caron ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Fate ◽

Protein Interactions ◽

In Silico ◽

Inverse Correlation ◽

Ros Production ◽

Gene Encoding ◽

Specific Expression ◽

Novel Approach ◽

Stress Dependent

Abstract Background Oxidative stress is a hallmark of many cancers. The increment in reactive oxygen species (ROS), resulting from an increased mitochondrial respiration, is the major cause of oxidative stress. Cell fate is known to be intricately linked to the amount of ROS produced. The direct generation of ROS is also one of the mechanisms exploited by common anticancer therapies, such as chemotherapy. Methods We assessed the role of NFKBIA with various approaches, including in silico analyses, RNA-silencing and xenotransplantation. Western blot analyses, immunohistochemistry and RT-qPCR were used to detect the expression of specific proteins and genes. Immunoprecipitation and pull-down experiments were used to evaluate protein-protein interactions. Results Here, by using an in silico approach, following the identification of NFKBIA (the gene encoding IκBα) amplification in various cancers, we described an inverse correlation between IκBα, oxidative metabolism, and ROS production in lung cancer. Furthermore, we showed that novel IκBα targeting compounds combined with cisplatin treatment promote an increase in ROS beyond the tolerated threshold, thus causing death by oxytosis. Conclusions NFKBIA amplification and IκBα overexpression identify a unique cancer subtype associated with specific expression profile and metabolic signatures. Through p65-NFKB regulation, IκBα overexpression favors metabolic rewiring of cancer cells and distinct susceptibility to cisplatin. Lastly, we have developed a novel approach to disrupt IκBα/p65 interaction, restoring p65-mediated apoptotic responses to cisplatin due to mitochondria deregulation and ROS-production.

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Systemic oxidative stress is associated with lower aerobic capacity and impaired skeletal muscle energy metabolism in heart failure patients

Scientific Reports ◽

10.1038/s41598-021-81736-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Takashi Yokota ◽

Shintaro Kinugawa ◽

Kagami Hirabayashi ◽

Mayumi Yamato ◽

Shingo Takada ◽

...

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Skeletal Muscle ◽

Energy Metabolism ◽

Aerobic Capacity ◽

Plantar Flexion ◽

Exercise Intolerance ◽

Whole Body ◽

Resonance Spectroscopy ◽

Systemic Oxidative Stress

AbstractOxidative stress plays a role in the progression of chronic heart failure (CHF). We investigated whether systemic oxidative stress is linked to exercise intolerance and skeletal muscle abnormalities in patients with CHF. We recruited 30 males: 17 CHF patients, 13 healthy controls. All participants underwent blood testing, cardiopulmonary exercise testing, and magnetic resonance spectroscopy (MRS). The serum thiobarbituric acid reactive substances (TBARS; lipid peroxides) were significantly higher (5.1 ± 1.1 vs. 3.4 ± 0.7 μmol/L, p < 0.01) and the serum activities of superoxide dismutase (SOD), an antioxidant, were significantly lower (9.2 ± 7.1 vs. 29.4 ± 9.7 units/L, p < 0.01) in the CHF cohort versus the controls. The oxygen uptake (VO2) at both peak exercise and anaerobic threshold was significantly depressed in the CHF patients; the parameters of aerobic capacity were inversely correlated with serum TBARS and positively correlated with serum SOD activity. The phosphocreatine loss during plantar-flexion exercise and intramyocellular lipid content in the participants' leg muscle measured by 31phosphorus- and 1proton-MRS, respectively, were significantly elevated in the CHF patients, indicating abnormal intramuscular energy metabolism. Notably, the skeletal muscle abnormalities were related to the enhanced systemic oxidative stress. Our analyses revealed that systemic oxidative stress is related to lowered whole-body aerobic capacity and skeletal muscle dysfunction in CHF patients.

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Serum Albumin Redox States: More than Oxidative Stress Biomarker

Antioxidants ◽

10.3390/antiox10040503 ◽

2021 ◽

Vol 10 (4) ◽

pp. 503

Author(s):

Fuka Tabata ◽

Yasuaki Wada ◽

Satomi Kawakami ◽

Kazuhiro Miyaji

Keyword(s):

Oxidative Stress ◽

Serum Albumin ◽

Animal Studies ◽

Redox State ◽

Ex Vivo ◽

Pathological Condition ◽

Analytical Techniques ◽

Cysteine Residue ◽

Research Field ◽

Systemic Oxidative Stress

Serum albumin is the most abundant circulating protein in mammals including humans. It has three isoforms according to the redox state of the free cysteine residue at position 34, named as mercaptalbumin (reduced albumin), non-mercaptalbumin-1 and -2 (oxidized albumin), respectively. The serum albumin redox state has long been viewed as a biomarker of systemic oxidative stress, as the redox state shifts to a more oxidized state in response to the severity of the pathological condition in various diseases such as liver diseases and renal failures. However, recent ex vivo studies revealed oxidized albumin per se could aggravate the pathological conditions. Furthermore, the possibility of the serum albumin redox state as a sensitive protein nutrition biomarker has also been demonstrated in a series of animal studies. A paradigm shift is thus ongoing in the research field of the serum albumin. This article provides an updated overview of analytical techniques for serum albumin redox state and its association with human health, focusing on recent findings.

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Contribution of Adipose Tissue Oxidative Stress to Obesity-Associated Diabetes Risk and Ethnic Differences: Focus on Women of African Ancestry

Antioxidants ◽

10.3390/antiox10040622 ◽

2021 ◽

Vol 10 (4) ◽

pp. 622

Author(s):

Pamela A. Nono Nankam ◽

Télesphore B. Nguelefack ◽

Julia H. Goedecke ◽

Matthias Blüher

Keyword(s):

Oxidative Stress ◽

Adipose Tissue ◽

Metabolic Diseases ◽

African Ancestry ◽

Fat Distribution ◽

African Women ◽

European Ancestry ◽

Whole Body ◽

Redox Equilibrium ◽

Systemic Oxidative Stress

Adipose tissue (AT) storage capacity is central in the maintenance of whole-body homeostasis, especially in obesity states. However, sustained nutrients overflow may dysregulate this function resulting in adipocytes hypertrophy, AT hypoxia, inflammation and oxidative stress. Systemic inflammation may also contribute to the disruption of AT redox equilibrium. AT and systemic oxidative stress have been involved in the development of obesity-associated insulin resistance (IR) and type 2 diabetes (T2D) through several mechanisms. Interestingly, fat accumulation, body fat distribution and the degree of how adiposity translates into cardio-metabolic diseases differ between ethnicities. Populations of African ancestry have a higher prevalence of obesity and higher T2D risk than populations of European ancestry, mainly driven by higher rates among African women. Considering the reported ethnic-specific differences in AT distribution and function and higher levels of systemic oxidative stress markers, oxidative stress is a potential contributor to the higher susceptibility for metabolic diseases in African women. This review summarizes existing evidence supporting this hypothesis while acknowledging a lack of data on AT oxidative stress in relation to IR in Africans, and the potential influence of other ethnicity-related modulators (e.g., genetic-environment interplay, socioeconomic factors) for consideration in future studies with different ethnicities.

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Oxidative stress-dependent contribution of HMGB1 to the interplay between apoptosis and autophagy in diabetic rat liver

Journal of Physiology and Biochemistry ◽

10.1007/s13105-017-0574-0 ◽

2017 ◽

Vol 73 (4) ◽

pp. 511-521 ◽

Cited By ~ 15

Author(s):

Anja Petrović ◽

Desanka Bogojević ◽

Aleksandra Korać ◽

Igor Golić ◽

Sofija Jovanović-Stojanov ◽

...

Keyword(s):

Oxidative Stress ◽

Rat Liver ◽

Diabetic Rat ◽

Stress Dependent

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Oxidative stress increases megalin expression in the renal proximal tubules during the normoalbuminuric stage of diabetes mellitus

AJP Renal Physiology ◽

10.1152/ajprenal.00108.2017 ◽

2018 ◽

Vol 314 (3) ◽

pp. F462-F470 ◽

Cited By ~ 5

Author(s):

Yoshifumi Kurosaki ◽

Akemi Imoto ◽

Fumitaka Kawakami ◽

Masanori Yokoba ◽

Tsuneo Takenaka ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Hydrogen Peroxide ◽

High Glucose ◽

Renal Cortex ◽

Dependent Manner ◽

Phosphatidylinositol 3 Kinase ◽

Phosphorylated Akt ◽

Stress Dependent ◽

Phosphatidylinositol 3

Megalin, an endocytic receptor expressed in proximal tubule cells, plays a critical role in renal tubular protein reabsorption and is associated with the albuminuria observed in diabetic nephropathy. We have previously reported increased oxidant production in the renal cortex during the normoalbuminuric stage of diabetes mellitus (DM); however, the relationship between oxidative stress and renal megalin expression during the normoalbuminuric stage of DM remains unclear. In the present study, we evaluated whether oxidative stress affects megalin expression in the normoalbuminuric stage of DM in a streptozotocin-induced diabetic rat model and in immortalized human proximal tubular cells (HK-2). We demonstrated that increased expression of renal megalin accompanies oxidative stress during the early stage of DM, before albuminuria development. Telmisartan treatment prevented the diabetes-induced elevation in megalin level, possibly through an oxidative stress-dependent mechanism. In HK-2 cells, hydrogen peroxide significantly increased megalin levels in a dose- and time-dependent manner; however, the elevation in megalin expression was decreased following prolonged exposure to severe oxidative stress induced by 0.4 mmol/l hydrogen peroxide. High-glucose treatment also significantly increased megalin expression in HK-2 cells. Concurrent administration of the antioxidant N-acetyl-cysteine blocked the effects of high glucose on megalin expression. Furthermore, the hydrogen peroxide-induced increase in megalin expression was blocked by treatment with phosphatidylinositol 3-kinase and Akt inhibitors. Increase of phosphorylated Akt expression was also seen in the renal cortex of diabetic rats. Taken together, our results indicate that mild oxidative stress increases renal megalin expression through the phosphatidylinositol 3-kinase-Akt pathway in the normoalbuminuric stage of DM.

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