Antero Salminen

University of Eastern Finland, Kuopio, Eastern Finland Province, Finland

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Publications (242)778.22 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose Endocannabinoid receptors have been suggested to be a possible therapeutical target in age-related diseases. Particularly CB2, the receptor primarily responsible for the immune modulatory effects of cannabinoids, might be a valuable target in diseases, such as age-related macular degeneration, where inflammation is known to be a key player. In this study, we have evaluated the effects of CB2 activation on the viability and inflammatory response of retinal pigment epithelial cells.Methods We cultured ARPE-19 cells until confluent and treated the cells with the selective CB2 agonist JWH-133. To assess the effect of CB2 activation on oxidatively stressed cells we treated some cells with the lipid peroxidation end product 4-Hydroxynonenal (HNE) after the JWH-133 stimulation. The effects of the treatments on cell viability were assessed and inflammatory cytokine expression and signaling protein activation were measured by ELISA.Results Our results show that 10µM JWH-133 robustly increased the production of interleukin (IL) 6 and IL-8 in both HNE-treated and untreated cells. Investigation of the MAPK signaling pathway showed that JWH-133 at this concentration increased the phosphorylation of ERK1/2.Conclusion Our results show that JWH-133, a selective agonist of the cannabinoid receptor CB2, stimulates an inflammatory response in ARPE-19 cells. The release of inflammatory cytokines seems to be mediated by the increased activity of the MAPKinase ERK1/2. Taken together, our results suggest that CB2’s role as a potential therapeutical target in retinal pigment epithelium should be more carefully analyzed in future studies.
    Acta ophthalmologica 09/2014; 92(s253). · 2.44 Impact Factor
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    ABSTRACT: Histone methylation is involved in the epigenetic control of immune responses and cellular senescence. Jumonji domain-containing protein 3 (JMJD3), also called lysine-specific demethylase 6B (KDM6b), is an inducible histone demethylase which enhances immune responses and can trigger cellular senescence. JMJD3 potentiates gene expression by demethylating repressive H3K27me3 epigenetic marks in promoters and gene bodies. Moreover, JMJD3 also stimulates transcription in a demethylase-independent manner by mediating interactions between chromatin modifiers. JMJD3 can enhance both pro-inflammatory and anti-inflammatory responses by targeting distinct transcription factors in a context-dependent manner in gene promoters. For instance, JMJD3 can induce macrophage M2 polarization via STAT6 signaling. JMJD3 also interacts with T-bet factor and induces Th1 differentiation of CD4(+) T cells. Moreover, JMJD3 can activate TGF-β signaling through the SMAD3 pathway. Conversely, JMJD3 displaces polycomb complexes from the INK4 box, which induces the expression of INK4a and triggers cellular senescence. JMJD3 can also enhance the nuclear localization of p53 and thus regulate its function. The control of INK4 box and p53 is closely related to the regulation of the aging process. We will briefly review the inducible properties of JMJD3 expression and then focus on the role of JMJD3 in the regulation of inflammation and senescence through different signaling pathways. We emphasize that an inflammatory milieu and cellular stress can enhance immune responses and provoke cellular senescence via epigenetic regulation through JMJD3 activation.
    Journal of molecular medicine (Berlin, Germany). 06/2014;
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    ABSTRACT: Abstract Age-related macular degeneration (AMD) is a multifactorial eye disease that is associated with aging, family history, smoking, obesity, cataract surgery, arteriosclerosis, hypertension, hypercholesterolemia and unhealthy diet. Gender has commonly been classified as a weak or inconsistent risk factor for AMD. This disease is characterized by degeneration of retinal pigment epithelial (RPE) cells, Bruch's membrane, and choriocapillaris, which secondarily lead to damage and death of photoreceptor cells and central visual loss. Pathogenesis of AMD involves constant oxidative stress, chronic inflammation, and increased accumulation of lipofuscin and drusen. Estrogen has both anti-oxidative and anti-inflammatory capacity and it regulates signaling pathways that are involved in the pathogenesis of AMD. In this review, we discuss potential cellular signaling targets of estrogen in retinal cells and AMD pathology.
    Current eye research. 06/2014;
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    ABSTRACT: Many aging theories have proposed that mitochondria and energy metabolism have a major role in the aging process. There are recent studies indicating that Krebs cycle intermediates can shape the epigenetic landscape of chromatin by regulating DNA and histone methylation. A growing evidence indicates that epigenetics plays an important role in the regulation of healthspan but also is involved in the aging process. 2-Oxoglutarate (α-ketoglutarate) is a key metabolite in the Krebs cycle but it is also an obligatory substrate for 2-oxoglutarate-dependent dioxygenases (2-OGDO). The 2-OGDO enzyme family includes the major enzymes of DNA and histone demethylation, i.e. Ten-Eleven Translocation (TETs) and Jumonji C domain containing (JmjC) demethylases. In addition, 2-OGDO members can regulate collagen synthesis and hypoxic responses in a non-epigenetical manner. Interestingly, succinate and fumarate, also Krebs cycle intermediates, are potent inhibitors of 2-OGDO enzymes, i.e. the balance of Krebs cycle reactions can affect the level of DNA and histone methylation and thus control gene expression. We will review the epigenetic mechanisms through which Krebs cycle intermediates control the DNA and histone methylation. We propose that age-related disturbances in the Krebs cycle function induce stochastic epigenetic changes in chromatin structures which in turn promote the aging process.
    Ageing research reviews. 06/2014;
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    ABSTRACT: Although there is a substantial literature that mitochondria have a crucial role in the aging process, the mechanism has remained elusive. The role of reactive oxygen species, mitochondrial DNA injuries, and a decline in mitochondrial quality control has been proposed. Emerging studies have demonstrated that Krebs cycle intermediates, 2-oxoglutarate (also known as α-ketoglutarate), succinate and fumarate, can regulate the level of DNA and histone methylation. Moreover, citrate, also a Krebs cycle metabolite, can enhance histone acetylation. Genome-wide screening studies have revealed that the aging process is linked to significant epigenetic changes in the chromatin landscape, e.g. global demethylation of DNA and histones and increase in histone acetylation. Interestingly, recent studies have revealed that the demethylases of DNA (TET1-3) and histone lysines (KDM2-7) are members of 2-oxoglutarate-dependent dioxygenases (2-OGDO). The 2-OGDO enzymes are activated by oxygen, iron and the major Krebs cycle intermediate, 2-oxoglutarate, whereas they are inhibited by succinate and fumarate. Considering the endosymbiont origin of mitochondria, it is not surprising that Krebs cycle metabolites can control the gene expression of host cell by modifying the epigenetic landscape of chromatin. It seems that age-related disturbances in mitochondrial metabolism can induce epigenetic reprogramming, which promotes the appearance of senescent phenotype and degenerative diseases.
    Cellular Signalling 04/2014; · 4.47 Impact Factor
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    ABSTRACT: The modulation of protein deacetylase SIRT1 has a vast therapeutic potential in treatment of several aging-associated diseases. Active regulator of SIRT1 (AROS) is a small endogenous protein which was originally reported to activate SIRT1 through a direct interaction in cancer cells. We show that the interaction between the two proteins is weak and does not alter the activity of SIRT1 in non-cancerous human cells. The results of different in vitro SIRT1 activity assays disclosed AROS as an inhibitor of SIRT1. The functional relationship between AROS and SIRT1 proved to be dependent on the biological context and experimental setting.
    FEBS letters 03/2014; · 3.54 Impact Factor
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    ABSTRACT: Age-related macular degeneration (AMD) is characterized primarily by degeneration of the macular retinal pigment epithelium (RPE) that secondarily leads to cell death of photoreceptors and impaired central vision. Hallmarks of AMD are accumulation of lysosomal lipofuscin and extracellular drusen, which indicate impaired proteolysis in RPE cells. Cellular proteostasis is strongly regulated by molecular chaperones such as Hsp70 and proteasomal and autophagic clearance systems. We have recently shown that autophagy receptor SQSTM1/p62 binds irreversibly to proteasome inhibitor-induced perinuclear protein aggregates and undergoes autophagic clearance in RPE cell cultures. Revealing decreased autophagy, SQSTM1/p62 accumulates in macular area of donor AMD patient samples. In this study, we show that Hsp70 binds reversibly to proteasome inhibitor-induced perinuclear protein aggregates and does not become degraded by autophagy in ARPE-19 cells. Our observation reveals new opportunities to use a cytoprotective Hsp70 as a therapy target in the prevention of RPE cell degeneration and development of AMD.
    Journal of Biochemical and Pharmacological Research. 03/2014; 2(1):1-7.
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    ABSTRACT: Age-related macular degeneration (AMD) is characterized primarily by degeneration of the macular retinal pigment epithelium (RPE) that secondarily leads to cell death of photoreceptors and impaired central vision. Hallmarks of AMD are accumulation of lysosomal lipofuscin and extracellular drusen, which indicate impaired proteolysis in RPE cells. Cellular proteostasis is strongly regulated by molecular chaperones such as Hsp70 and proteasomal and autophagic clearance systems. We have recently shown that autophagy receptor SQSTM1/p62 binds irreversibly to proteasome inhibitor-induced perinuclear protein aggregates and undergoes autophagic clearance in RPE cell cultures. Revealing decreased autophagy, SQSTM1/p62 accumulates in macular area of donor AMD patient samples. In this study, we show that Hsp70 binds reversibly to proteasome inhibitor-induced perinuclear protein aggregates and does not become degraded by autophagy in ARPE-19 cells. Our observation reveals new opportunities to use a cytoprotective Hsp70 as a therapy target in the prevention of RPE cell degeneration and development of AMD.
    Journal of Biochemical and Pharmacological Research. 03/2014; 2(1):33-43.
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    ABSTRACT: Processing of misfolded proteins is important in order for the cell to maintain its normal functioning and homeostasis. Three systems control the quality of proteins: chaperone-mediated refolding, proteasomal degradation of ubiquitinated proteins, and finally, when the two others fail, aggrephagy, as selective form of autophagy, degrades ubiquitin-labelled aggregated cargos. In this route misfolded proteins gradually form larger aggregates, aggresomes and they eventually become double membrane-wrapped organelles called autophagosomes, which become degraded when they fuse to lysosomes, for reuse by the cell. The stages, the main molecules participating in the process, and the regulation of aggrephagy are discussed here, as is the role of protein aggregation in protein accumulation diseases. In particular, we emphasize that both Alzheimer's disease and age-related macular degeneration, two of the most common pathologies in the aged, are characterized by altered protein clearance and deposits. Based on the hypothesis that manipulations of autophagy may be potentially useful in these and other aggregation-related diseases, we will discuss some promising therapeutic strategies to counteract protein aggregates-induced cellular toxicity.
    Ageing Research Reviews. 01/2014;
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    ABSTRACT: Chronic inflammation and oxidative stress (OS) are present in Alzheimer's disease (AD) brains in addition to neuronal loss, Amyloid-β (Aβ) plaques and hyperphosphorylated tau-protein neurofibrillary tangles (NFTs). Previously we showed that levels of the pro-inflammatory cytokine, interleukin-18 (IL-18), are elevated in post-mortem AD brains. IL-18 can modulate the tau kinases, Cdk5 and GSK3β, as well as Aβ-production. IL-18 levels are also increased in AD risk diseases, including type-2 diabetes and obesity. Here, we explored other IL-18 regulated proteins in neuron-like SH-SY5Y cells. Differentiated SH-SY5Y cells, incubated with IL-18 for 24, 48, or 72 h, were analyzed by two-dimensional gel electrophoresis (2D-DIGE). Specific altered protein spots were chosen and identified with mass spectrometry (MS) and verified by western immunoblotting (WIB). IL-18 had time-dependent effects on the SH-SY5Y proteome, modulating numerous protein levels/modifications. We concentrated on those related to OS (DDAH2, peroxiredoxins 2, 3, and 6, DJ-1, BLVRA), Aβ-degradation (MMP14, TIMP2), Aβ-aggregation (Septin-2), and modifications of axon growth and guidance associated, collapsin response mediator protein 2 (CRMP2). IL-18 significantly increased antioxidative enzymes, indicative of OS, and altered levels of glycolytic α- and γ-enolase and multifunctional 14-3-3γ and -ε, commonly affected in neurodegenerative diseases. MMP14, TIMP2, α-enolase and 14-3-3ε, indirectly involved in Aβ metabolism, as well as Septin-2 showed changes that increase Aβ levels. Increased 14-3-3γ may contribute to GSK3β driven tau hyperphosphorylation and CRMP2 Thr514 and Ser522 phosphorylation with the Thr555-site, a target for Rho kinase, showing time-dependent changes. IL-18 also increased caspase-1 levels and vacuolization of the cells. Although our SH-SY5Y cells were not aged, as neurons in AD, our work suggests that heightened or prolonged IL-18 levels can drive protein changes of known relevance to AD pathogenesis.
    Frontiers in Cellular Neuroscience 01/2014; 8:214. · 4.47 Impact Factor
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    ABSTRACT: Inflammation is a major mechanism of acute brain injury and chronic neurodegeneration. This neuroinflammation is known to be substantially regulated by the transcription factor NF-κB, which is predominantly found in the form of heterodimer of p65 (RelA) and p50 subunit, with p50/p50 homodimers being also common. The p65 subunit has a transactivation domain, whereas p50 is chiefly involved in DNA binding. Binding of the p65/p50 heterodimers are thought to induce expression of numerous proinflammatory genes in microglia. Here we show that cultured microglia deficient for the gene (Nfkb1) encoding p50 subunit show reduced induction of proinflammatory mediators, increased expression of anti-inflammatory genes, and increased expression of CD45, an immunoregulatory molecule, in response to lipopolysaccharide (LPS) exposure, but increased capacity to take up β-amyloid (Aβ) which is associated with enhanced release of tumor necrosis factor alpha (TNFα). However, Nfkb1 deficiency strongly increases leukocyte infiltration and the expression of proinflammatory genes in response to intrahippocampal administration of LPS. Also, when crossing Nfkb1 deficient mice with APdE9 transgenic mice the expression of proinflammatory genes was strongly enhanced, whereas Aβ burden was slightly but significantly reduced. These alterations in expression of inflammatory mediators in Nfkb1 deficient mice were associated with reduced expression of CD45. Our data demonstrates a crucial and complex role p50 subunit of NF-κB in brain inflammation, especially in regulating the phenotype of microglia after acute and chronic inflammatory insults relevant to clinical conditions, contributing to both pro-inflammatory and anti-inflammatory responses of microglia, infiltration of leukocytes, and clearance of Aβ in Alzheimer's disease.
    Neurobiology of Disease 12/2013; · 5.62 Impact Factor
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    ABSTRACT: Cloning studies have revealed that the apoptosis-associated speck-like protein possessing a caspase-recruiting domain (ASC) and the target of methylation-induced silencing-1 (TMS) are identical proteins. ASC/TMS1 is a bipartite adaptor protein containing the N-terminal pyrin domain and the C-terminal caspase-recruitment domain. There is abundant literature on ASC/TMS1, mostly under the name TMS1, in the epigenetic regulation of apoptosis and carcinogenesis, whereas the abbreviation ASC has been adopted from studies on the assembly of inflammasomes and stimulation of inflammation. There is substantial literature emphasizing that there are common aspects in the regulation of apoptosis and inflammation, which may be related to the function of ASC/TMS1. The region of the transcription start site of ASC/TMS1 gene contains a 600-bp-long CpG island that is highly methylated and the transcription of ASC/TMS1 is repressed in several cancers. However, it is not known whether the ASC/TMS1-dependent epigenetic regulation controls the inflammasome functions and moreover whether this regulation has any role in the inflammation-mediated carcinogenesis or in the pathogenesis of age-related degenerative diseases. We will examine the mechanisms involved in the epigenetic regulation of ASC/TMS1 as well as their significance in the coordination of apoptosis and inflammasome functions. We will also review the role of aberrant methylation of ASC/TMS1 promoter in the function of inflammasomes, a major host defense system, in cellular housekeeping and carcinogenesis.
    Cellular and Molecular Life Sciences CMLS 11/2013; · 5.62 Impact Factor
  • Antero Salminen, Anu Kauppinen, Kai Kaarniranta
    11/2013: pages 323-330; , ISBN: 9780123978073
  • Anu Kauppinen, Antero Salminen, Kai Kaarniranta
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    ABSTRACT: Minocycline is a wide-spectrum antibiotic derived from tetracycline. In addition to its anti-microbial activity, minocycline is known to possess several immunomodulatory and neuroprotective properties. Fewer severe side effects and more efficient tissue penetration make minocycline better than its parent tetracycline. Doxycycline competes with minocycline in improved biological half-life but minocycline becomes more rapidly absorbed in tissues than doxycycline. Due to its high lipid solubility, minocycline also crosses the blood-brain barrier easily, which increases its relevance in the treatment of diseases beyond the barriers. Inflammasomes are intracellular protein complexes which become primed via NF-kB and MAPK pathways, and activated by various PAMPs and DAMPs. In this article, we hypothese about the capability of minocycline to regulate inflammasomes as part of its anti-inflammatory activity. The hypothesis is based on the ability of minocycline to regulate signals essential to both the priming and the activation of inflammasome signaling.
    Inflammasome. 11/2013; 1:2-14.
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    ABSTRACT: Purpose Age-related macular degeneration (AMD) is the most prominent cause of severe vision loss in western countries. Inflammation is known to play a central role in the pathogenesis of AMD but the mechanisms are still largerly unknown. Lately, the novel signaling pathway of intracellular multi-protein complexes called inflammasomes has been associated with the disease. In addition to inflammation, decline in the intracellular cleaning systems, i.e. autophagy and proteasomal degradation, is another hallmark of AMD. In the present study, we have studied the cross-talk between NLRP3 inflammasomes and autophagy. Methods ARPE-19 cells were grown into confluence and exposed to the proteasome inhibitor MG-132. Thereafter, Bafilomycin A was added and the cell cultures were incubated for another 24 hours. Results Our results show that the inhibition of lysosome acidification by Bafilomycin A increased the release of inflammasome-related cytokine IL-1 in MG-132-treated ARPE-19 cells. In addition, the amounts of inflammasome receptor and adaptor proteins, i.e. NLRP3 and ASC, respectively, as well as the activity of the executive Caspase-1 enzyme were increased. Conclusion Our present results suggest that intracellular protein aggregates could induce the inflammasome activation in ARPE-19 cells especially in circumstances where autophagy is declined.
    Acta ophthalmologica 08/2013; 91(s252). · 2.44 Impact Factor
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    ABSTRACT: Purpose Age-related macular degeneration(AMD) is the leading cause of blindness in the western world. And despite extensive research many questions about disease progression and formation still remain unanswered. One of the driving factors of AMD is a chronic inflammatory process, stimulated by life-long exposure to light and oxidative stress. In the current study we try to evaluate the anti-inflammatory properties of Quercetin, a plant derived polyphenol, and to determine the pathways by which it inhibits inflammation. Methods Cultured ARPE-19 cells were treated with the lipid peroxidation endproduct 4-Hydroxynonenal (HNE) to induce an inflammatory response. Quercetin was added 1 hour after stimulation with HNE to assess its power to suppress an already activated inflammatory response. The effects of the treatment on intracellular inflammation were measured with ELISA and quantitative Real-Time PCR. Cell viability was assessed using the lactate dehydrogenase (LDH)-assay. Results Our results show that Quercetin decreased the levels of the pro-inflammatory cytokines MCP-1 and IL-8. It also protected the cells from HNE-induced toxicity, as was evidenced by a decrease in LDH levels. Quercetin lowered the levels of mitogen-activated protein kinase (MAP) p38 and of phospho-CREB but did not affect the levels of NF-κB or the DNA binding efficacy of its subunit p65. Conclusion Our results show that Quercetin can reduce the inflammatory response in retinal pigment epithelial cells by down regulating the MAPK pathway and decreasing the phosphorylation of CREB. Furthermore it is able to protect cells from death induced by oxidative stress. Quercetin may, therefore, be a valuable tool in the therapy of inflammation in AMD.
    Acta ophthalmologica 08/2013; 91(s252). · 2.44 Impact Factor
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    ABSTRACT: Purpose Autophagy and proteasomal degradation, two central clearance systems of the cell, decline during aging. Increased amount of protein aggregates and other waste material compromise normal cellular functions. Inflammasomes are intracellular protein complexes which can become activated by diverse danger signals. It has recently been shown that a decline in cellular clearance systems can offer a sufficient signal for the inflammasome activation. In the present study, we have studied the effects of impaired proteasomal degradation and autophagy on inflammation in ARPE-19 cells. Methods In order to inhibit the proteasomal degradation and autophagy, ARPE-19 cells were treated with MG-132 and Bafilomycin A1, respectively. Productions of IL-1b and IL-8 were measured using ELISA method. Results Our data shows that MG-132 increases the productions of IL-1b and IL-8. The addition of Bafilomycin A1 further increases the amount of IL-1b but not that of IL-8. Conclusion Our data suggests that intracellular protein aggregates are capable of inducing inflammation through several pathways. Production of IL-1b indicates the activation of inflammasome signaling. Interestingly, the inflammasome signaling seems to become further enhanced when autophagy is blocked in addition to proteasomes. Meanwhile, the production of IL-8 remains at the same level.
    Acta ophthalmologica 08/2013; 91(s252). · 2.44 Impact Factor
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    ABSTRACT: The accumulation of amyloid-β-containing neuritic plaques and intracellular tau protein tangles are key histopathological hallmarks of Alzheimer's disease (AD). This type of pathology clearly indicates that the mechanisms of neuronal housekeeping and protein quality control are compromised in AD. There is mounting evidence that the autophagosome-lysosomal degradation is impaired, which could disturb the processing of APP and provoke AD pathology. Beclin 1 is a molecular platform assembling an interactome with stimulating and suppressive components which regulate the initiation of the autophagosome formation. Recent studies have indicated that the expression Beclin 1 is reduced in AD brain. Moreover, the deficiency of Beclin 1 in cultured neurons and transgenic mice provokes the deposition of amyloid-β peptides whereas its overexpression reduces the accumulation of amyloid-β. There are several potential mechanisms, which could inhibit the function of Beclin 1 interactome and thus impair autophagy and promote AD pathology. The mechanisms include (i) reduction of Beclin 1 expression or its increased proteolytic cleavage by caspases, (ii) sequestration of Beclin 1 to non-functional locations, such as tau tangles, (iii) formation of inhibitory complexes between Beclin 1 and antiapoptotic Bcl-2 proteins or inflammasomes, (iv) interaction of Beclin 1 with inhibitory neurovirulent proteins, e.g. herpex simplex ICP34.5, or (v) inhibition of the Beclin 1/Vps34 complex through the activation of CDK1 and CDK5. We will shortly introduce the function of Beclin 1 interactome in autophagy and phagocytosis, review the recent evidence indicating that Beclin 1 regulates autophagy and APP processing in AD, and finally examine the potential mechanisms through which Beclin 1 dysfunction could be involved in the pathogenesis of AD.
    Progress in Neurobiology 07/2013; · 9.04 Impact Factor
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    ABSTRACT: Recent studies have indicated that the regulation of innate immunity and energy metabolism are connected together through an antagonistic crosstalk between NF-κB and SIRT1 signaling pathways. NF-κB signaling has a major role in innate immunity defence while SIRT1 regulates the oxidative respiration and cellular survival. However, NF-κB signaling can stimulate glycolytic energy flux during acute inflammation, whereas SIRT1 activation inhibits NF-κB signaling and enhances oxidative metabolism and the resolution of inflammation. SIRT1 inhibits NF-κB signaling directly by deacetylating the p65 subunit of NF-κB complex. SIRT1 stimulates oxidative energy production via the activation of AMPK, PPARα and PGC-1α and simultaneously, these factors inhibit NF-κB signaling and suppress inflammation. On the other hand, NF-κB signaling down-regulates SIRT1 activity through the expression of miR-34a, IFNγ, and reactive oxygen species. The inhibition of SIRT1 disrupts oxidative energy metabolism and stimulates the NF-κB-induced inflammatory responses present in many chronic metabolic and age-related diseases. We will examine the molecular mechanisms of the antagonistic signaling between NF-κB and SIRT1 and describe how this crosstalk controls inflammatory process and energy metabolism. In addition, we will discuss how disturbances in this signaling crosstalk induce the appearance of chronic inflammation in metabolic diseases.
    Cellular Signalling 06/2013; · 4.47 Impact Factor
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    ABSTRACT: Age-related macular degeneration (AMD) is a complex, degenerative and progressive disease involving multiple genetic and environmental factors. It can result in severe visual loss e.g. AMD is the leading cause of blindness in the elderly in the western countries. Although age, genetics, diet, smoking, and many cardiovascular factors are known to be linked with this disease there is increasing evidence that long-term oxidative stress, impaired autophagy clearance and inflammasome mediated inflammation are involved in the pathogenesis. Under certain conditions these may trigger detrimental processes e.g. release of vascular endothelial growth factor (VEGF), causing choroidal neovascularisation e.g. in wet AMD. This review ties together these crucial pathological threads in AMD.
    The international journal of biochemistry & cell biology 04/2013; · 4.89 Impact Factor

Publication Stats

5k Citations
778.22 Total Impact Points

Institutions

  • 2010–2014
    • University of Eastern Finland
      • • Department of Neurology
      • • Institute of Clinical Medicine
      • • School of Medicine
      Kuopio, Eastern Finland Province, Finland
  • 2001–2014
    • Kuopio University Hospital
      • • Department of Ophthalmology
      • • Department of Neurology
      Kuopio, Eastern Finland Province, Finland
  • 2013
    • University Medical Center Schleswig-Holstein
      Kiel, Schleswig-Holstein, Germany
  • 2012–2013
    • University of Lodz
      • Department of Molecular Genetics
      Łódź, Lodz Voivodeship, Poland
  • 1996–2011
    • University of Kuopio
      • • Department of Neurology
      • • Department of Ophthalmology
      Kuopio, Eastern Finland Province, Finland
  • 1988–2009
    • University of Turku
      • • Department of Biology
      • • Department of Pathology
      Turku, Western Finland, Finland
  • 1977–2009
    • University of Jyväskylä
      • • Division of Cell and Molecular Biology
      • • Department of Biological and Environmental Science
      • • Muscle Damage Research Area
      Jyväskylä, Province of Western Finland, Finland
  • 1991
    • National Institutes of Health
      • Laboratory of Cell Biology
      Bethesda, MD, United States
  • 1990
    • National Cancer Institute (USA)
      • Laboratory of Cell Biology
      Maryland, United States
  • 1986–1990
    • University of Oulu
      • Department of Paediatrics
      Oulu, Oulu, Finland