An association between polymorphism of the heme oxygenase-1 and -2 genes and age-related macular degeneration

Synowiec, Ewelina; Szaflik, Jerzy; Chmielewska, Marta; Woźniak, Katarzyna; Sklodowska, Anna; Waszczyk, Maja; Dorecka, Mariola; Błasiak, Janusz; Szaflik, Jacek P.

doi:10.1007/s11033-011-0955-3

Cited by 28 publications

(27 citation statements)

References 43 publications

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“…On the other hand, HO-2 is constitutively expressed and is not induced by factors that induce HO-1 expression; its expression is believed to assist in creating a basal tone of anti-inflammatory signals 4, 18 . A study by Synowiec et al, show a correlation between age-related macular degeneration and polymorphisms of the heme oxygenase -1 and -2 genes, clearly indicating that a fully functional heme oxygenase system is crucial for long term eye health 36 . We observed in pterygia that expression of HO-1 is significantly reduced compared to the control tissue despite the presence of several known HO-1 inducing cytokines, chemokines, growth factors 37, 38 and evidence of damage from oxidative stress 39, 40 .…”

Section: Discussionmentioning

confidence: 99%

Dysregulated Heme Oxygenase–Ferritin System in Pterygium Pathogenesis

Fox

Gotlinger

Dunn

et al. 2013

Cornea

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Purpose Cyclooxygenases (COX), lipoxygenases (LOX) and cytochrome P450 monooxygenases (CYP) derived eicosanoids have been implicated in ocular surface inflammation and neovascularization. These eicosanoids are subjected to regulation by enzymes such as heme oxygenases (HO) and ferritin. Methods Quantitative PCR and LC-MS/MS based lipidomics were performed on pterygia from patients undergoing surgical pterygium excision. Control tissues consisted of donor corneas. In addition, LC-MS/MS-based lipidomics was performed on tears collected from patients prior to surgery. Results mRNA-expression of HO-2, the constitutive HO isoform, was upregulated by 40 % in pterygia as compared to control tissue, while the mRNA level of the inducible form, HO-1, was downregulated by more than 50 %. Levels of CYP4B1 mRNA showed an approximate 2-fold increase in pterygia compared to control. Lipidomics analysis of tissues indicated a doubling in PGE2 and TxB2 levels in pterygia as compared to control. Among LOX-derived metabolites, the anti-inflammatory 15-HETE levels were significantly reduced in pterygia (79.3±48.11 pg/mg protein) as compared to control (586.2±213.5 pg/mg protein), whereas pro-inflammatory LOX- and CYP4B1-derived 12-HETE levels were 10-fold higher in pterygia (2768±832.3 pg/mg protein) compared to control (231.4±87.35 pg/mg protein). PGE2 and the HETEs were also present in tears from patients with a pterygium, but were not detected in tears from healthy volunteers. Ferritin light and heavy chain mRNA expression levels were 60 % and 30 % lower in pterygia as compared to control. Conclusion We believe a dysfunctional HO-Ferritin system leads to increased levels of proinflammatory mediators, thus contributing to the inflammation characteristic of pterygia.

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Section: Discussionmentioning

confidence: 99%

Dysregulated Heme Oxygenase–Ferritin System in Pterygium Pathogenesis

Fox

Gotlinger

Dunn

et al. 2013

Cornea

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“…(Chowers et al, 2006; Wong et al, 2007) To date, the genetic studies to establish a role of iron metabolism in AMD have been relatively weak. Nearly all of the recent studies of possible associations of transferrin and heme oxygenase-1 and -2 genes have come from a single group (Synowiec et al, 2011; Wysokinski et al, 2011a; Wysokinski et al, 2011b) and replication from larger cohorts has not been done. However, given the critical nature of iron metabolic pathways for the human body, one should not exclude the potential role of these genes in AMD.…”

Section: 0 Genetics-based Causality Of Amdmentioning

confidence: 99%

Genetic insights into age-related macular degeneration: Controversies addressing risk, causality, and therapeutics

Gorin

2012

Molecular Aspects of Medicine

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Age-related macular degeneration (AMD) is a common condition among the elderly population that leads to the progressive central vision loss and serious compromise of quality of life for its sufferers. It is also one of the few disorders for whom the investigation of its genetics has yielded rich insights into its diversity and causality and holds the promise of enabling clinicians to provide better risk assessments for individuals as well as to develop and selectively deploy new therapeutics to either prevent or slow the development of disease and lessen the threat of vision loss. The genetics of AMD began initially with the appreciation of familial aggregation and increase risk and expanded with the initial association of APOE variants with the disease. The first major breakthroughs came with family-based linkage studies of affected (and discordant) sibs, which identified a number of genetic loci and led to the targeted search of the 1q31 and 10q26 loci for associated variants. Three of the initial four reports for the CFH variant, Y402H, were based on regional candidate searches, as were the two initial reports of the ARMS2/HTRA1 locus variants. Case-control association studies initially also played a role in discovering the major genetic variants for AMD, and the success of those early studies have been used to fuel enthusiasm for the methodology for a number of diseases. Until 2010, all of the subsequent genetic variants associated with AMD came from candidate gene testing based on the complement factor pathway. In 2010, several large-scale genome-wide association studies (GWAS) identified genes that had not been previously identified. Much of this historical information is available in a number of recent reviews.(Chen et al., 2010b; Deangelis et al., 2011; Fafowora and Gorin, 2012b; Francis and Klein, 2011; Kokotas et al., 2011) Large meta analysis of AMD GWAS has added new loci and variants to this collection.(Chen et al., 2010a; Kopplin et al., 2010; Yu et al., 2011) This paper will focus on the ongoing controversies that are confronting AMD genetics at this time, rather than attempting to summarize this field, which has exploded in the past 5 years.

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“…Meanwhile, among the upregulated proteins, NDUFA2, a mitochondrial complex I subcomplex, may inhibit ROS generation (Li et al, 2013). HMOX2 is an important marker of iron‐related oxidative stress and is part of an important defense mechanism against oxidative stress (Synowiec et al, 2012). Similarly, a study has demonstrated that CYB5R3 also can protect cells from oxidative stress (Siendones et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

FAM96B inhibits the senescence of dental pulp stem cells

Liang

Yang

et al. 2020

Cell Biology International

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Dental pulp stem cells (DPSCs) are considered a remarkable source for the regeneration of dental pulp tissues, but their therapeutic effectiveness remains limited, especially in elderly people. Previous studies found that senescence has a negative effect on the proliferation and differentiation potential of DPSCs. Moreover, numerous long non-coding RNA (lncRNA) and messenger RNA were significantly differentially regulated in DPSCs from young and elderly donors. However, the changes in DPSCs protein during senescence have not been addressed. In this study, differences in DPSC protein expression profiles and coexpression of protein and lncRNA were analyzed using proteomics and bioinformatics. The results showed 75 upregulated proteins and 69 downregulated proteins in DPSCs from elderly donors. Vasopressin-regulated water reabsorption, Parkinson's disease, Alzheimer's disease, and protein export were the top four functional pathways associated with DPSCs. High mobility group N1 (HMGN1), HMGN2, UCHL1, and the family with sequence similarity 96 member B homeobox gene (FAM96B) were associated with DPSCs senescence. Then, we investigated FAM96B function in DPSCs. After FAM96B depletion, telomerase reverse transcriptase (TERT) activity decreased, but the number of senescence-associated β-galactosidase (SA-β-gal) positive cells and the protein levels of p16, p53 were significantly increased. Gain-of-function assays suggested that FAM96B overexpression was positively correlated with TERT activity, but negatively correlated with the number of SA-β-gal positive cells and the protein levels of P16 and P53. Moreover, after FAM96B overexpression, the results showed a significant increase in alkaline phosphatase activity and an enhanced mineralization ability of DPSCs. The reverse-transcription polymerase chain reaction results also showed that dentin sialophosphoprotein and osteocalcin were expressed at greater levels. The carboxyfluorescein succinimidyl ester (CFSE) results displayed that FAM96B increased the proliferation potential of DPSCs. Our study revealed candidate proteins that might be related to DPSCs senescence and provided information to elucidate the mechanism of the biological changes in DPSCs' aging. Moreover, FAM96B was demonstrated to play an important role in suppressing DPSCs senescence and promoting osteogenic differentiation and proliferation.Abbreviations: DPSCs, dental pulp stem cells; FAM96B, the family with sequence similarity 96 member B homeobox gene; MSCs, mesenchymal stem cells; shRNAs, short-hairpin RNAs; TERT, telomerase reverse transcriptase † Hanbing Liang and Wenzhi Li contributed equally to this work.

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An association between polymorphism of the heme oxygenase-1 and -2 genes and age-related macular degeneration

Cited by 28 publications

References 43 publications

Dysregulated Heme Oxygenase–Ferritin System in Pterygium Pathogenesis

Dysregulated Heme Oxygenase–Ferritin System in Pterygium Pathogenesis

Genetic insights into age-related macular degeneration: Controversies addressing risk, causality, and therapeutics

FAM96B inhibits the senescence of dental pulp stem cells

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