About: Role of ER stress response in photodynamic therapy: ROS generated in different subcellular compartments trigger diverse cell death pathways

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rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
Description	We have analyzed the molecular mechanisms of photoinduced cell death using porphyrins with similar structure differing only in the position of the ethylene glycol (EG) chain on the phenyl ring. Meta-and para-positioned EG chains targeted porphyrins to different subcellular compartments. After photoactivation, both types of derivatives induced death of tumor cells via reactive oxygen species (ROS). Para derivatives pTPP(EG) 4 and pTPPF(EG) 4 primarily accumulated in lysosomes activated the p38 MAP kinase cascade, which in turn induced the mitochondrial apoptotic pathway. In contrast, meta porphyrin derivative mTPP(EG) 4 localized in the endoplasmic reticulum (ER) induced dramatic changes in Ca2+ homeostasis manifested by Ca2+ rise in the cytoplasm, activation of calpains and stress caspase-12 or caspase-4. ER stress developed into unfolded protein response. Immediately after irradiation the PERK pathway was activated through phosphorylation of PERK, eIF2 alpha and induction of transcription factors ATF4 and CHOP, which regulate stress response genes. PERK knockdown and PERK deficiency protected cells against mTPP(EG) 4-mediated apoptosis, confirming the causative role of the PERK pathway. We have analyzed the molecular mechanisms of photoinduced cell death using porphyrins with similar structure differing only in the position of the ethylene glycol (EG) chain on the phenyl ring. Meta-and para-positioned EG chains targeted porphyrins to different subcellular compartments. After photoactivation, both types of derivatives induced death of tumor cells via reactive oxygen species (ROS). Para derivatives pTPP(EG) 4 and pTPPF(EG) 4 primarily accumulated in lysosomes activated the p38 MAP kinase cascade, which in turn induced the mitochondrial apoptotic pathway. In contrast, meta porphyrin derivative mTPP(EG) 4 localized in the endoplasmic reticulum (ER) induced dramatic changes in Ca2+ homeostasis manifested by Ca2+ rise in the cytoplasm, activation of calpains and stress caspase-12 or caspase-4. ER stress developed into unfolded protein response. Immediately after irradiation the PERK pathway was activated through phosphorylation of PERK, eIF2 alpha and induction of transcription factors ATF4 and CHOP, which regulate stress response genes. PERK knockdown and PERK deficiency protected cells against mTPP(EG) 4-mediated apoptosis, confirming the causative role of the PERK pathway. (en)
Title	Role of ER stress response in photodynamic therapy: ROS generated in different subcellular compartments trigger diverse cell death pathways Role of ER stress response in photodynamic therapy: ROS generated in different subcellular compartments trigger diverse cell death pathways (en)
skos:prefLabel	Role of ER stress response in photodynamic therapy: ROS generated in different subcellular compartments trigger diverse cell death pathways Role of ER stress response in photodynamic therapy: ROS generated in different subcellular compartments trigger diverse cell death pathways (en)
skos:notation	RIV/68378050:_____/12:00387879!RIV13-GA0-68378050
http://linked.open...avai/predkladatel	Ústav molekulární genetiky AV ČR, v. v. i.
http://linked.open...avai/riv/aktivita	P Z
http://linked.open...avai/riv/aktivity	P(GA203/09/1311), P(GAP303/11/1291), P(LC06077), Z(AV0Z50520514)
http://linked.open...iv/cisloPeriodika	3
http://linked.open...vai/riv/dodaniDat	2013
http://linked.open...aciTvurceVysledku	Králová, Jarmila Moserová, Irena
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Ústav molekulární genetiky AV ČR, v. v. i.
http://linked.open...dnocenehoVysledku	165997
http://linked.open...ai/riv/idVysledku	RIV/68378050:_____/12:00387879
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	photodynamic therapy; porphyrin derivatives; cell death; ER stress (en)
http://linked.open.../riv/klicoveSlovo	porphyrin derivatives cell death photodynamic therapy ER stress
http://linked.open...odStatuVydavatele	US - Spojené státy americké
http://linked.open...ontrolniKodProRIV	[0B9E2816B2E7]
http://linked.open...i/riv/nazevZdroje	PLoS ONE
http://linked.open...in/vavai/riv/obor	EB
http://linked.open...ichTvurcuVysledku	2 (xsd:int)
http://linked.open...cetTvurcuVysledku	2 (xsd:int)
http://linked.open...vavai/riv/projekt	Synthetic probes for recognition of tumor markers:applications for cell directed apoptosis and targeted photodynamic therapy New types of ligands interfering with cancer cell communication as a new therapeutic strategy Center of Chemical Genetics
http://linked.open...UplatneniVysledku	2012
http://linked.open...v/svazekPeriodika	7
http://linked.open...iv/tvurceVysledku	Králová, Jarmila Moserová, Irena
http://linked.open...ain/vavai/riv/wos	000303017700128
http://linked.open...n/vavai/riv/zamer	Molekulárně genetické a buněčné základy klíčových biologických procesů: genová exprese, onkogeneze, replikace virů, imunita a vývoj organismů
issn	1932-6203
number of pages	16 (xsd:int)
http://bibframe.org/vocab/doi	10.1371/journal.pone.0032972
is http://linked.open...avai/riv/vysledek of	Role of ER stress response in photodynamic therapy: ROS generated in different subcellular compartments trigger diverse cell death pathways

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