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We are analyzing https://link.springer.com/article/10.1007/s00204-016-1835-3.

Title:
Bilirubin-induced ER stress contributes to the inflammatory response and apoptosis in neuronal cells | Archives of Toxicology
Description:
Unconjugated bilirubin (UCB) in newborns may lead to bilirubin neurotoxicity. Few studies investigated the activation of endoplasmic reticulum stress (ER stress) by UCB. We performed an in vitro comparative study using undifferentiated SH-SY5Y, differentiated GI-ME-N neuronal cells and human U87 astrocytoma cells. ER stress and its contribution to inflammation and apoptosis induced by UCB were analyzed. Cytotoxicity, ER stress and inflammation were observed only in neuronal cells, despite intracellular UCB accumulation in all three cell types. UCB toxicity was enhanced in undifferentiated SH-SY5Y cells and correlated with a higher mRNA expression of pro-apoptotic CHOP. Mouse embryonic fibroblast knockout for CHOP and CHOP siRNA-silenced SH-SY5Y increased cells viability upon UCB exposure. In SH-SY5Y, ER stress inhibition by 4-phenylbutyric acid reduced UCB-induced apoptosis and decreased the cleaved forms of caspase-3 and PARP proteins. Reporter gene assay and PERK siRNA showed that IL-8 induction by UCB is transcriptionally regulated by NFкB and PERK signaling. These data suggest that ER stress has an important role in the UCB-induced inflammation and apoptosis, and that targeting ER stress may represent a potential therapeutic approach to decrease UCB-induced neurotoxicity.
Website Age:
28 years and 1 months (reg. 1997-05-29).

Matching Content Categories {📚}

  • Education
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What CMS is link.springer.com built with?

Custom-built

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🌠 Phenomenal Traffic: 5M - 10M visitors per month


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Keywords {🔍}

article, pubmed, google, scholar, cas, stress, cell, bilirubin, endoplasmic, reticulum, cells, response, unconjugated, death, central, activation, bilirubininduced, neuronal, tiribelli, neurotoxicity, apoptosis, ucb, inflammation, mol, content, qaisiya, med, author, privacy, cookies, toxicity, cristina, shsyy, chop, signaling, access, pathway, molecular, biol, brain, authors, data, publish, research, search, mohammed, jašprová, libor, vitek, bellarosa,

Topics {✒️}

month download article/chapter jana jašprová bilirubin-induced neurologic damage–mechanisms libor vitek author information authors decrease ucb-induced neurotoxicity author correspondence bilirubin-induced cns injury humanized udp-glucuronosyltransferase1 mice signaling regulator grp78/bip bilirubin-induced neurologic dysfunction undifferentiated sh-sy5y cells bilirubin-induced immunostimulant effects brain mitochondrial membranes–dependence bilirubin-induced neurotoxicity er stress-induced inflammation endoplasmic reticulum ca2 + release nfкb induces er stress full article pdf bilirubin oxidation-specific induction pro-apoptotic chop undifferentiated sh-sy5y fondazione italiana fegato bilirubin metabolism research rat brain regions privacy choices/manage cookies cell death induced targeting er stress er stress reaches check access instant access ip3 receptors contributes er stress inhibition endoplasmic reticulum stress higher mrna expression cyp mrna expression area science park unfolded protein response vivo cellular adaptation cytochrome p450 2a5 perk sirna showed cristina brischetto bilirubin neurotoxicity reporter gene assay neonatal hippocampal neurons related subjects jaundiced gunn rats cultured astrocytes neuronal cell death

Questions {❓}

  • Garg AD et al (2012) ER stress-induced inflammation: does it aid or impede disease progression?
  • Malhotra JD, Kaufman RJ (2007) Endoplasmic reticulum stress and oxidative stress: a vicious cycle or a double-edged sword?

Schema {🗺️}

WebPage:
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         description:Unconjugated bilirubin (UCB) in newborns may lead to bilirubin neurotoxicity. Few studies investigated the activation of endoplasmic reticulum stress (ER stress) by UCB. We performed an in vitro comparative study using undifferentiated SH-SY5Y, differentiated GI-ME-N neuronal cells and human U87 astrocytoma cells. ER stress and its contribution to inflammation and apoptosis induced by UCB were analyzed. Cytotoxicity, ER stress and inflammation were observed only in neuronal cells, despite intracellular UCB accumulation in all three cell types. UCB toxicity was enhanced in undifferentiated SH-SY5Y cells and correlated with a higher mRNA expression of pro-apoptotic CHOP. Mouse embryonic fibroblast knockout for CHOP and CHOP siRNA-silenced SH-SY5Y increased cells viability upon UCB exposure. In SH-SY5Y, ER stress inhibition by 4-phenylbutyric acid reduced UCB-induced apoptosis and decreased the cleaved forms of caspase-3 and PARP proteins. Reporter gene assay and PERK siRNA showed that IL-8 induction by UCB is transcriptionally regulated by NFкB and PERK signaling. These data suggest that ER stress has an important role in the UCB-induced inflammation and apoptosis, and that targeting ER stress may represent a potential therapeutic approach to decrease UCB-induced neurotoxicity.
         datePublished:2016-08-30T00:00:00Z
         dateModified:2016-08-30T00:00:00Z
         pageStart:1847
         pageEnd:1858
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            ER stress
            4-PBA
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            Environmental Health
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                        name:Department of Medical Sciences, University of Trieste, Trieste, Italy
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      headline:Bilirubin-induced ER stress contributes to the inflammatory response and apoptosis in neuronal cells
      description:Unconjugated bilirubin (UCB) in newborns may lead to bilirubin neurotoxicity. Few studies investigated the activation of endoplasmic reticulum stress (ER stress) by UCB. We performed an in vitro comparative study using undifferentiated SH-SY5Y, differentiated GI-ME-N neuronal cells and human U87 astrocytoma cells. ER stress and its contribution to inflammation and apoptosis induced by UCB were analyzed. Cytotoxicity, ER stress and inflammation were observed only in neuronal cells, despite intracellular UCB accumulation in all three cell types. UCB toxicity was enhanced in undifferentiated SH-SY5Y cells and correlated with a higher mRNA expression of pro-apoptotic CHOP. Mouse embryonic fibroblast knockout for CHOP and CHOP siRNA-silenced SH-SY5Y increased cells viability upon UCB exposure. In SH-SY5Y, ER stress inhibition by 4-phenylbutyric acid reduced UCB-induced apoptosis and decreased the cleaved forms of caspase-3 and PARP proteins. Reporter gene assay and PERK siRNA showed that IL-8 induction by UCB is transcriptionally regulated by NFкB and PERK signaling. These data suggest that ER stress has an important role in the UCB-induced inflammation and apoptosis, and that targeting ER stress may represent a potential therapeutic approach to decrease UCB-induced neurotoxicity.
      datePublished:2016-08-30T00:00:00Z
      dateModified:2016-08-30T00:00:00Z
      pageStart:1847
      pageEnd:1858
      sameAs:https://doi.org/10.1007/s00204-016-1835-3
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         Environmental Health
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            name:Mohammed Qaisiya
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                  address:
                     name:Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS, Trieste, Italy
                     type:PostalAddress
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            email:[email protected]
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            name:Cristina Brischetto
            affiliation:
                  name:Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS
                  address:
                     name:Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS, Trieste, Italy
                     type:PostalAddress
                  type:Organization
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                  name:Charles University in Prague
                  address:
                     name:Institute of Medical Biochemistry and Laboratory Medicine, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic
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                  address:
                     name:Institute of Medical Biochemistry and Laboratory Medicine, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic
                     type:PostalAddress
                  type:Organization
                  name:Charles University in Prague
                  address:
                     name:4th Department of Internal Medicine, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Claudio Tiribelli
            affiliation:
                  name:Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS
                  address:
                     name:Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS, Trieste, Italy
                     type:PostalAddress
                  type:Organization
                  name:University of Trieste
                  address:
                     name:Department of Medical Sciences, University of Trieste, Trieste, Italy
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Cristina Bellarosa
            affiliation:
                  name:Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS
                  address:
                     name:Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS, Trieste, Italy
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      name:Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS
      address:
         name:Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS, Trieste, Italy
         type:PostalAddress
      name:Charles University in Prague
      address:
         name:Institute of Medical Biochemistry and Laboratory Medicine, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic
         type:PostalAddress
      name:Charles University in Prague
      address:
         name:Institute of Medical Biochemistry and Laboratory Medicine, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic
         type:PostalAddress
      name:Charles University in Prague
      address:
         name:4th Department of Internal Medicine, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic
         type:PostalAddress
      name:Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS
      address:
         name:Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS, Trieste, Italy
         type:PostalAddress
      name:University of Trieste
      address:
         name:Department of Medical Sciences, University of Trieste, Trieste, Italy
         type:PostalAddress
      name:Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS
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         name:Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS, Trieste, Italy
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               name:Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS, Trieste, Italy
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      name:Cristina Brischetto
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            name:Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS
            address:
               name:Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS, Trieste, Italy
               type:PostalAddress
            type:Organization
      name:Jana Jašprová
      affiliation:
            name:Charles University in Prague
            address:
               name:Institute of Medical Biochemistry and Laboratory Medicine, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic
               type:PostalAddress
            type:Organization
      name:Libor Vitek
      affiliation:
            name:Charles University in Prague
            address:
               name:Institute of Medical Biochemistry and Laboratory Medicine, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic
               type:PostalAddress
            type:Organization
            name:Charles University in Prague
            address:
               name:4th Department of Internal Medicine, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic
               type:PostalAddress
            type:Organization
      name:Claudio Tiribelli
      affiliation:
            name:Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS
            address:
               name:Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS, Trieste, Italy
               type:PostalAddress
            type:Organization
            name:University of Trieste
            address:
               name:Department of Medical Sciences, University of Trieste, Trieste, Italy
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            type:Organization
      name:Cristina Bellarosa
      affiliation:
            name:Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS
            address:
               name:Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS, Trieste, Italy
               type:PostalAddress
            type:Organization
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      name:Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS, Trieste, Italy
      name:Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS, Trieste, Italy
      name:Institute of Medical Biochemistry and Laboratory Medicine, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic
      name:Institute of Medical Biochemistry and Laboratory Medicine, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic
      name:4th Department of Internal Medicine, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic
      name:Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS, Trieste, Italy
      name:Department of Medical Sciences, University of Trieste, Trieste, Italy
      name:Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS, Trieste, Italy
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