Sucrose non-fermenting AMPK related kinase/Pentraxin 3 and DNA damage axis: a gateway to cardiovascular disease in systemic lupus erythematosus among Egyptian patients

Zineldeen, Doaa H.; Keshk, Walaa Arafa; Ghazy, Ahmed; El-Barbary, Amal Mohamed

doi:10.1177/0004563215578190

Cited by 13 publications

(4 citation statements)

References 50 publications

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“…Likewise, an increase in DNA damage levels by double-stranded DNA break has been found in peripheral lymphocytes in SLE patients with high levels of anti-La/SSB and anti-RNP antibodies compared to SLE patients without these antibodies [ 68 ] suggesting a pathogenic role. A potential explanation for this damage could rely on a prooxidant/antioxidant imbalance which increases the plasma concentrations of malondialdehyde, a marker of oxidative stress, as well as by the decrease in the activity of the superoxide dismutase enzyme in these patients [ 69 ].…”

Section: Dna Damage In Slementioning

confidence: 99%

DNA Damage and Deficiencies in the Mechanisms of Its Repair: Implications in the Pathogenesis of Systemic Lupus Erythematosus

Mireles-Canales

González-Chávez

Quiñonez-Flores

et al. 2018

Journal of Immunology Research

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Systemic lupus erythematosus (SLE) is a perplexing and potentially severe disease, the pathogenesis of which is yet to be understood. SLE is considered to be a multifactorial disease, in which genetic factors, immune dysregulation, and environmental factors, such as ultraviolet radiation, are involved. Recently, the description of novel genes conferring susceptibility to develop SLE even in their own (monogenic lupus) has raised the interest in DNA dynamics since many of these genes are linked to DNA repair. Damage to DNA induces an inflammatory response and eventually triggers an immune response, including those targeting self-antigens. We review the evidence that indicates that patients with SLE present higher levels of DNA damage than normal subjects do and that several proteins involved in the preservation of the genomic stability show polymorphisms, some of which increase the risk for SLE development. Also, the experience from animal models reinforces the connection between DNA damage and defective repair in the development of SLE-like disease including characteristic features such as anti-DNA antibodies and nephritis. Defining the role of DNA damage response in SLE pathogenesis might be strategic in the quest for novel therapies.

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Section: Dna Damage In Slementioning

confidence: 99%

DNA Damage and Deficiencies in the Mechanisms of Its Repair: Implications in the Pathogenesis of Systemic Lupus Erythematosus

Mireles-Canales

González-Chávez

Quiñonez-Flores

et al. 2018

Journal of Immunology Research

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“…Our demonstrated AICAR effects on SNARK expression were due to NF-κB inhibition and are kinase-independent due to the lack of SNARK enzymatic activation by AICAR [ 47 ]. The observed nuclear predominance of hepatic SNARK immunoreactivity is attributed to lipotoxic, oxidative, and ER stress, which drive its nuclear translocation [ 48 ]. SNARK activates hepatic yes-associated protein (YAP)/Hippo signaling, which plays a role in how NAFLD develops into NASH [ 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

AICAR Ameliorates Non-Alcoholic Fatty Liver Disease via Modulation of the HGF/NF-κB/SNARK Signaling Pathway and Restores Mitochondrial and Endoplasmic Reticular Impairments in High-Fat Diet-Fed Rats

Zineldeen

Tahoon

Sarhan

2023

IJMS

Self Cite

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Non-alcoholic fatty liver disease (NAFLD) is a global health problem characterized by altered lipid and redox homeostasis, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress. The AMP-dependent kinase (AMPK) agonist 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) has been shown to improve the outcome of NAFLD in the context of AMPK activation, yet the underlying molecular mechanism remains obscure. This study investigated the potential mechanism(s) of AICAR to attenuate NAFLD by exploring AICAR’s effects on the HGF/NF-κB/SNARK axis and downstream effectors as well as mitochondrial and ER derangements. High-fat diet (HFD)-fed male Wistar rats were given intraperitoneal AICAR at 0.7 mg/g body weight or left untreated for 8 weeks. In vitro steatosis was also examined. ELISA, Western blotting, immunohistochemistry and RT-PCR were used to explore AICAR’s effects. NAFLD was confirmed by steatosis score, dyslipidemia, altered glycemic, and redox status. HGF/NF-κB/SNARK was downregulated in HFD-fed rats receiving AICAR with improved hepatic steatosis and reduced inflammatory cytokines and oxidative stress. Aside from AMPK dominance, AICAR improved hepatic fatty acid oxidation and alleviated the ER stress response. In addition, it restored mitochondrial homeostasis by modulating Sirtuin 2 and mitochondrial quality gene expression. Our results provide a new mechanistic insight into the prophylactic role of AICAR in the prevention of NAFLD and its complications.

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“…In this meta-analysis, minimizing GV is accompanied by a reduction of IMT with an estimated magnitude between 0.09 and 0.47 mm, which is consistent with an estimated 11% to 59% reduction in risk of myocardial infarction and a 13% to 70% reduction in risk of stroke [ 24 ]. Meanwhile, some studies found that IMT was associated with Phosphoinositide 3-kinase (PI3K) [ 25 ] and AMPK pathway [ 26 ], suggesting GV possibly affect IMT through PI3K or AMPK pathway.…”

Section: Discussionmentioning

confidence: 99%

Glucose variability for cardiovascular risk factors in type 2 diabetes: a meta-analysis

Liang

Yin

Wei

et al. 2017

J Diabetes Metab Disord

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AimsIt is consensus that glucose variability (GV) plays an important role in maccomplications of type 2 diabetes, but whether GV has a causal role is not yet clear for cardiovascular disease (CVD). This study sought to explore the effect on GV for CVD risk factors with type 2 diabetes.MethodsThe systematic literature search was performed to identify all GV and CVD risk factors, including total cholesterol (TC), LDL cholesterol (LDL-C), triglyceride (TG), HDL cholesterol (HDL-C), Body Mass Index (BMI), waist circumference (WC), High-Sensitivity C-reactive protein (Hs-CRP), Homeostasis model assessment (HOMA) and carotid intima-media thickness (IMT). Preferred Reporting Items was synthesized for Systematic reviews and Meta Analyses guideline. And the pooled analyses were undertaken using Review Manager 5.3.ResultsTwenty two studies were included with a total of 1143 patients in high glucose variability group (HGVG) and 1275 patients low glucose variability group (LGVG). Among these selected CVD risk factors, HOMA-IR and reduced IMT were affected by GV. HOMA-IR level was significantly lower in LGVG than in HGVG (MD = 0.58, 95% CI: 0.26 to 0.91, P = 0.0004), with evidence of heterogeneity between studies (I2 = 0%; P = 0.47).Reduced IMT level was significantly lower in LGVG than in HGVG (SMD = 0.28, 95% CI: 0.09 to 0.47, P = 0.003), with evidence of heterogeneity between studies (I2 = 0%; P = 0.48). However, the others were no significant statistical difference.ConclusionsAmong these selected CVD risk factors in type 2 diabetes, minimizing GV could improve insulin resistance and reduced IMT, consistent with a lowering in risk of CVD.Electronic supplementary materialThe online version of this article (10.1186/s40200-017-0323-5) contains supplementary material, which is available to authorized users.

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Sucrose non-fermenting AMPK related kinase/Pentraxin 3 and DNA damage axis: a gateway to cardiovascular disease in systemic lupus erythematosus among Egyptian patients

Cited by 13 publications

References 50 publications

DNA Damage and Deficiencies in the Mechanisms of Its Repair: Implications in the Pathogenesis of Systemic Lupus Erythematosus

DNA Damage and Deficiencies in the Mechanisms of Its Repair: Implications in the Pathogenesis of Systemic Lupus Erythematosus

AICAR Ameliorates Non-Alcoholic Fatty Liver Disease via Modulation of the HGF/NF-κB/SNARK Signaling Pathway and Restores Mitochondrial and Endoplasmic Reticular Impairments in High-Fat Diet-Fed Rats

Glucose variability for cardiovascular risk factors in type 2 diabetes: a meta-analysis

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