Carbofuran affects cellular autophagy and developmental senescence through the impairment of Nrf2 signalling

Khan, Alam; Zaman, Tanjeena; Fahad, Talukdar Mohammad; Akther, Tanjima; Hasan, Faruk; Naz, Tarannum; Kishi, Shuji

doi:10.1111/jcmm.16774

Cited by 13 publications

(8 citation statements)

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“…Moreover, prolonged ROS production activates the NRF2/antioxidant responsive element (ARE) pathway, implicated in detoxification, through NRF2 phosphorylation and translocation to the nucleus, leading to transcription regulation of NRF2 target genes. Several of these genes are involved in the antioxidant response, such as Cat , Sod-1 , and Hmox-1 among others [ 63 , 64 , 65 ]. Some evidence shows that cellular senescence is directly associated with NRF2 pathway impairment, since overactivation of the NRF2 pathway decreases the expression of some senescence markers, such as p21 [ 63 ], whereas NRF2 inhibition produces cellular senescence [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

“…Several of these genes are involved in the antioxidant response, such as Cat , Sod-1 , and Hmox-1 among others [ 63 , 64 , 65 ]. Some evidence shows that cellular senescence is directly associated with NRF2 pathway impairment, since overactivation of the NRF2 pathway decreases the expression of some senescence markers, such as p21 [ 63 ], whereas NRF2 inhibition produces cellular senescence [ 64 ]. Different preclinical studies have demonstrated an impairment of the NRF2 antioxidant pathway in CKD.…”

Section: Discussionmentioning

confidence: 99%

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Oxidative Stress and Cellular Senescence Are Involved in the Aging Kidney

et al. 2022

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Chronic kidney disease (CKD) can be considered as a clinical model for premature aging. However, non-invasive biomarkers to detect early kidney damage and the onset of a senescent phenotype are lacking. Most of the preclinical senescence studies in aging have been done in very old mice. Furthermore, the precise characterization and over-time development of age-related senescence in the kidney remain unclear. To address these limitations, the age-related activation of cellular senescence-associated mechanisms and their correlation with early structural changes in the kidney were investigated in 3- to 18-month-old C57BL6 mice. Inflammatory cell infiltration was observed by 12 months, whereas tubular damage and collagen accumulation occurred later. Early activation of cellular-senescence-associated mechanisms was found in 12-month-old mice, characterized by activation of the DNA-damage-response (DDR), mainly in tubular cells; activation of the antioxidant NRF2 pathway; and klotho downregulation. However, induction of tubular-cell-cycle-arrest (CCA) and overexpression of renal senescent-associated secretory phenotype (SASP) components was only found in 18-month-old mice. In aging mice, both inflammation and oxidative stress (marked by elevated lipid peroxidation and NRF2 inactivation) remained increased. These findings support the hypothesis that prolonged DDR and CCA, loss of nephroprotective factors (klotho), and dysfunctional redox regulatory mechanisms (NRF2/antioxidant defense) can be early drivers of age-related kidney-damage progression.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Oxidative Stress and Cellular Senescence Are Involved in the Aging Kidney

et al. 2022

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“… 32–35 SPNS1, which encodes Spinster homologue 1 protein, is a transmembrane protein that can modulate the metabolism of autophagic lysosomal and critically associate with cellular ageing and survival. 36 37 Notably, SPNS1 has recently been considered as a core component of T cell receptor signalling. 38 A slew of studies have shown that TRIM10 and TRIM27 were involved in several inflammation processes.…”

Section: Discussionmentioning

confidence: 99%

“…Apart from this, ZNF322 can regulate the expression of two cell-cycle genes ( P27 and CDK2 ), which were characterised as crucial regulators involved in synoviocytes proliferation 32–35 . SPNS1, which encodes Spinster homologue 1 protein, is a transmembrane protein that can modulate the metabolism of autophagic lysosomal and critically associate with cellular ageing and survival 36 37. Notably, SPNS1 has recently been considered as a core component of T cell receptor signalling 38.…”

Section: Discussionmentioning

confidence: 99%

Novel insight into the aetiology of rheumatoid arthritis gained by a cross-tissue transcriptome-wide association study

Wang

Yin

et al. 2022

RMD Open

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BackgroundAlthough genome-wide association studies (GWASs) have identified more than 100 loci associated with rheumatoid arthritis (RA) susceptibility, the causal genes and biological mechanisms remain largely unknown.MethodsA cross-tissue transcriptome-wide association study (TWAS) using the unified test for molecular signaturestool was performed to integrate GWAS summary statistics from 58 284 individuals (14 361 RA cases and 43 923 controls) with gene-expression matrix in the Genotype-Tissue Expression project. Subsequently, a single tissue by using FUSION software was conducted to validate the significant associations. We also compared the TWAS with different gene-based methodologies, including Summary Data Based Mendelian Randomization (SMR) and Multimarker Analysis of Genomic Annotation (MAGMA). Further in silico analyses (conditional and joint analysis, differential expression analysis and gene-set enrichment analysis) were used to deepen our understanding of genetic architecture and comorbidity aetiology of RA.ResultsWe identified a total of 47 significant candidate genes for RA in both cross-tissue and single-tissue test after multiple testing correction, of which 40 TWAS-identified genes were verified by SMR or MAGMA. Among them, 13 genes were situated outside of previously reported significant loci by RA GWAS. Both TWAS-based and MAGMA-based enrichment analyses illustrated the shared genetic determinants among autoimmune thyroid disease, asthma, type I diabetes mellitus and RA.ConclusionOur study unveils 13 new candidate genes whose predicted expression is associated with risk of RA, providing new insights into the underlying genetic architecture of RA.

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“…Moreover, prolonged ROS production activates the NRF2/Are pathway, implicated in detoxification, through NRF2 phosphorylation and translocation to the nucleus, leading to the regulation of transcription of NRF2 target genes. Several of these genes are involved in the antioxidant response, such as Catalase, Sod-1, Hmox-1 and others (Khan et al, 2021;Ungvari et al, 2019;Yu et al, 2021). Some evidences show that cellular senescence is directly associated with NRF2 pathway impairment, since increased NRF2 pathway decreases senescence marker expression such as p21 (Yu et al, 2021) and its inhibition produces cellular senescence (Khan et al, 2021).…”

Section: Figure 10 Conceptual Representation Of Age-associated Mechan...mentioning

confidence: 99%

Senescent cell accumulation & Research-based undergraduate education

Valentijn¹

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Chapter 1 General introduction Chapter 2 Cellular senescence in the aging and diseased kidney Chapter 3 CCN2 aggravates acute DNA damage and the subsequent DDR-Senescence-Fibrosis sequence following renal ischemiareperfusion injury Chapter 4 CCN2 aggravates the immediate Oxidative Stress-DNA Damage Response following renal ischemia-reperfusion injury Chapter 5 Acute kidney injury is aggravated in aged mice by the exacerbation of proinflammatory processes Chapter 6 Oxidative stress and cellular senescence are involved in the aging kidney Chapter 7 A human conditionally immortalized proximal tubule epithelial cell line as a novel model for studying senescence and response to senolytics Chapter 8 Cellular senescence and the kidney: potential therapeutic targets and tools Chapter 9 Cellular senescence in kidney biopsies is associated with tubular dysfunction and predicts CKD progression in childhood cancer patients with KIN Bridging research (part 1) and education (part 2) Chapter 10 Proposal for a research-based bachelor course design to provide insight into underlying mechanisms of the rare, genetic renal disease KIN Part 2. Research-based education in undergraduate biomedicine education Chapter 11 A challenge-based interdisciplinary undergraduate concept fostering translational medicine Chapter 12 A novel undergraduate biomedical laboratory course concept in synergy with ongoing faculty research Chapter 13 Hybrid PhD tracks with synergy between education and research Chapter 14 Summarizing discussion and future perspectives Appendices Nederlandse samenvatting Dankwoord Curriculum vitae CHAPTER 1 General introductionChapter 1. General introduction Chronic kidney disease is a major health burden lacking effective treatment Chronic kidney disease (CKD) is a common, progressive and irreversible disorder. In 2016, the global prevalence of CKD was estimated to be 13.4%. In the Netherlands, the prevalence of CKD is estimated to be around 10%. (Nierstichting-a) People with CKD have an increased risk of end-stage kidney disease (ESKD) and cardiovascular disease. Lifestyle and drug interventions (e.g. ACE inhibition or angiotensin II receptor type 2 inhibition) are currently the cornerstone for treatment for CKD, but do not sufficiently prevent CKD progression. A large number of CKD patients (approximately 2000 patients per year in the Netherlands (Nierstichting-b)) develop ESKD and will need to switch to renal replacement therapy such as dialysis or transplantation. During dialysis, quality of life is poor and morbidity and mortality are high. ESRD patients who start dialysis between the ages of 45 and 65 have a 5-year survival rate of under 50% in the United States and Europe. (Robinson et al. 2016) Donor kidneys are scarce and long-term renal allograft survival is poor. The halflife of kidney transplants is approximately 9 years for deceased donor grafts and 12 years for living donor grafts. (Lamb et al. 2011) Thus, the demand for better treatment options to stop CKD progression and improve survival of a graft kidney i...

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Carbofuran affects cellular autophagy and developmental senescence through the impairment of Nrf2 signalling

Cited by 13 publications

References 61 publications

Oxidative Stress and Cellular Senescence Are Involved in the Aging Kidney

Oxidative Stress and Cellular Senescence Are Involved in the Aging Kidney

Novel insight into the aetiology of rheumatoid arthritis gained by a cross-tissue transcriptome-wide association study

Senescent cell accumulation & Research-based undergraduate education

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