FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W7163079> ?p ?o ?g. }

• W7163079 abstract "Loss of integrity of either the inner or outer mitochondrial membrane results in the dissipation of the mitochondrial electrochemical gradient that leads to mitochondrial membrane permeability transition (mMPT). This study emphasizes the role of glycogen synthase kinase 3beta (GSK-3β) in maintaining mitochondrial membrane potential, thus preventing mitochondrial depolarization (hereafter termed mitoprotection). Using 3-(2,4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (SB216763), an inhibitor of GSK-3β, and drawing a distinction between it and 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene (UO126), an inhibitor of extracellular-signal-regulated kinase (ERK) phosphorylation, the means by which GSK-3β influences mitoprotection in cultured human lens epithelial (HLE-B3) cells and normal, secondary cultures of bovine lens epithelial cells, maintained in atmospheric oxygen, was investigated.Virally transfected human lens epithelial cells (HLE-B3) and normal cultures of bovine lens epithelial cells were exposed to acute hypoxic conditions (about 1% O2) followed by exposure to atmospheric oxygen (about 21% O2). Specific antisera and western blot analysis was used to examine the state of phosphorylation of ERK and GSK-3β, as well as the phosphorylation of a downstream substrate of GSK-3β, glycogen synthase (GS, useful in monitoring GSK-3β activity). The potentiometric dye, 1H-benzimidazolium-5,6-dichloro-2-[3-(5,6-dichloro-1,3-diethyl-1,3-dihydro-2H-benzimidazol-2-ylidene)-1-propenyl]-1,3-diethyl-iodide (JC-1), was used to monitor mitochondrial depolarization upon exposure of inhibitor treatment relative to the control cells (mock inhibition) in atmospheric oxygen. Caspase-3 activation was scrutinized to determine whether mitochondrial depolarization inevitably leads to apoptosis.Treatment of HLE-B3 cells with SB216763 (12 µM) inactivated GSK-3β activity as verified by the enzyme's inability to phosphorylate its substrate, GS. SB216763-treated cells were not depolarized relative to the control cells as demonstrated with JC-1 fluorescent dye analysis. The HLE-B3 cells treated with UO126, which similarly blocked phosphorylation of GS, were nevertheless prone to mMPT relative to the control cells. Western blot analysis determined that Bcl-2-associated X (BAX) levels were unchanged for SB216763-treated or UO126-treated HLE-B3 cells when compared to their respective control cells. However, unlike the SB216763-treated cells, the UO126-treated cells showed a marked absence of Bcl-2, as well as phosphorylated Bcl-2 relative to the controls. UO126 treatment of bovine lens epithelial cells showed similar results with pBcl-2 levels, while the Bcl-2 content appeared unchanged relative to the control cells. HLE-B3 and normal bovine lens cell cultures showed susceptibility to mMPT associated with the loss of pBcl-2 by UO126 treatment.MITOCHONDRIAL DEPOLARIZATION MAY OCCUR BY ONE OF TWO KEY OCCURRENCES: interruption of the electrochemical gradient across the inner mitochondrial membrane resulting in mMPT or by disruption of the integrity of the inner or outer mitochondrial membrane. The latter scenario is generally tightly regulated by members of the Bcl-2 family of proteins. Inhibition of GSK-3β activity by SB216763 blocks mMPT by preventing the opening of the mitochondrial permeability transition pore. UO126, likewise, inhibits GSK-3β activity, but unlike SB216763, inhibition of ERK phosphorylation induces the loss of intracellular pBcl-2 levels under conditions where intracellular BAX levels remain constant. These results suggest that the lenticular mitoprotection normally afforded by the inactivation of GSK-3β activity may, however, be bypassed by a loss of pBcl-2, an anti-apoptotic member of the Bcl-2 family. Bcl-2 prevents the translocation of BAX to the mitochondrial outer membrane inhibiting depolarization by disrupting the normal electrochemical gradient leading to mMPT." @default.
• W7163079 created "2016-06-24" @default.
• W7163079 creator A5009214738 @default.
• W7163079 creator A5061046013 @default.
• W7163079 creator A5063122089 @default.
• W7163079 date "2013-01-01" @default.
• W7163079 modified "2023-09-23" @default.
• W7163079 title "Lenticular mitoprotection. Part B: GSK-3β and regulation of mitochondrial permeability transition for lens epithelial cells in atmospheric oxygen." @default.
• W7163079 cites W1823288226 @default.
• W7163079 cites W1898009824 @default.
• W7163079 cites W1940473922 @default.
• W7163079 cites W1965758611 @default.
• W7163079 cites W1970834072 @default.
• W7163079 cites W1974718425 @default.
• W7163079 cites W2008046168 @default.
• W7163079 cites W2015839591 @default.
• W7163079 cites W2028463380 @default.
• W7163079 cites W2030363519 @default.
• W7163079 cites W2044745267 @default.
• W7163079 cites W2048012950 @default.
• W7163079 cites W2052607700 @default.
• W7163079 cites W2054903524 @default.
• W7163079 cites W2059668731 @default.
• W7163079 cites W2062934426 @default.
• W7163079 cites W2079905944 @default.
• W7163079 cites W2107720674 @default.
• W7163079 cites W2117571600 @default.
• W7163079 cites W2146571452 @default.
• W7163079 cites W2148061274 @default.
• W7163079 cites W2153570396 @default.
• W7163079 cites W2158951763 @default.
• W7163079 cites W2160086057 @default.
• W7163079 cites W2163768568 @default.
• W7163079 cites W2317926428 @default.
• W7163079 cites W2415055161 @default.
• W7163079 cites W8128757 @default.
• W7163079 cites W97091009 @default.
• W7163079 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3850969" @default.
• W7163079 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24319338" @default.
• W7163079 hasPublicationYear "2013" @default.
• W7163079 type Work @default.
• W7163079 sameAs 7163079 @default.
• W7163079 citedByCount "3" @default.
• W7163079 countsByYear W71630792014 @default.
• W7163079 countsByYear W71630792015 @default.
• W7163079 countsByYear W71630792016 @default.
• W7163079 crossrefType "journal-article" @default.
• W7163079 hasAuthorship W7163079A5009214738 @default.
• W7163079 hasAuthorship W7163079A5061046013 @default.
• W7163079 hasAuthorship W7163079A5063122089 @default.
• W7163079 hasConcept C11960822 @default.
• W7163079 hasConcept C12554922 @default.
• W7163079 hasConcept C13591479 @default.
• W7163079 hasConcept C153911025 @default.
• W7163079 hasConcept C173358068 @default.
• W7163079 hasConcept C182996813 @default.
• W7163079 hasConcept C190283241 @default.
• W7163079 hasConcept C2775934118 @default.
• W7163079 hasConcept C28859421 @default.
• W7163079 hasConcept C31573885 @default.
• W7163079 hasConcept C4141045 @default.
• W7163079 hasConcept C55493867 @default.
• W7163079 hasConcept C75385678 @default.
• W7163079 hasConcept C86803240 @default.
• W7163079 hasConcept C95444343 @default.
• W7163079 hasConceptScore W7163079C11960822 @default.
• W7163079 hasConceptScore W7163079C12554922 @default.
• W7163079 hasConceptScore W7163079C13591479 @default.
• W7163079 hasConceptScore W7163079C153911025 @default.
• W7163079 hasConceptScore W7163079C173358068 @default.
• W7163079 hasConceptScore W7163079C182996813 @default.
• W7163079 hasConceptScore W7163079C190283241 @default.
• W7163079 hasConceptScore W7163079C2775934118 @default.
• W7163079 hasConceptScore W7163079C28859421 @default.
• W7163079 hasConceptScore W7163079C31573885 @default.
• W7163079 hasConceptScore W7163079C4141045 @default.
• W7163079 hasConceptScore W7163079C55493867 @default.
• W7163079 hasConceptScore W7163079C75385678 @default.
• W7163079 hasConceptScore W7163079C86803240 @default.
• W7163079 hasConceptScore W7163079C95444343 @default.
• W7163079 hasLocation W71630791 @default.
• W7163079 hasOpenAccess W7163079 @default.
• W7163079 hasPrimaryLocation W71630791 @default.
• W7163079 hasRelatedWork W1482216160 @default.
• W7163079 hasRelatedWork W1978291270 @default.
• W7163079 hasRelatedWork W1989621117 @default.
• W7163079 hasRelatedWork W1995717781 @default.
• W7163079 hasRelatedWork W2000293859 @default.
• W7163079 hasRelatedWork W2000864465 @default.
• W7163079 hasRelatedWork W2002209115 @default.
• W7163079 hasRelatedWork W2020076608 @default.
• W7163079 hasRelatedWork W2021354409 @default.
• W7163079 hasRelatedWork W2040339726 @default.
• W7163079 hasRelatedWork W2047837391 @default.
• W7163079 hasRelatedWork W2057574587 @default.
• W7163079 hasRelatedWork W2063221399 @default.
• W7163079 hasRelatedWork W2064513969 @default.
• W7163079 hasRelatedWork W2093123576 @default.
• W7163079 hasRelatedWork W2105988137 @default.
• W7163079 hasRelatedWork W2130784123 @default.

• next