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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.
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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?
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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
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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.
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