Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study photo-control of the non-biospecific interaction between endothelial cell membranes and photo-cation generatable water-soluble polymers were examined. The water-soluble polymers contained triphenylmethane leucohydroxide (malachite green) groups (contents: 0.4 and 1.6 mol%), which dissociate into triphenylmethyl cations and counter hydroxide ions upon ultraviolet light (UV) irradiation, and were prepared by free radical copolymerization of diphenyl(4-vinylphenyl)methane leucohydroxide and acrylamide. The nature and magnitude of the interaction was quantitatively assessed by direct luminescence measurement of the intracellular calcium ion concentration using a calcium-sensitive photoprotein, aequorin. When a PBS buffer of the photoreactive copolymers were added, prior to UV irradiation, to a PBS suspension of cultured bovine endothelial cells loaded with aequorin, no detectable elevation of Ca(2+) was measured. In contrast, cationic copolymers, derived from the photoreactive copolymers after UV irradiation at a wavelength of 290<lambda<410 nm, induced an immediate transient increase in the cytosolic free Ca(2+) concentration due to a Ca(2+) inflow from the extracellular space into the cells, which may be due to non-biospecific transmembrane stimulation. Longer UV irradiation exposures of the copolymers and higher concentrations of the polymers, with higher contents of the photodissociable group, resulted in more Ca(2+) inflow with little cellular damage. The photo-cation generatable copolymers developed here made possible to control the non-biospecific interaction with endothelial cell membranes by UV irradiation condition, and composition and amount of the copolymer.
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PMID:Photo-control of the interaction between endothelial cells and photo-cation generatable water-soluble polymers. 1271 45

1-(2-Chlorophenyl-N-methylpropyl)-3-isoquinolinecarboxamide (PK11195) is a proven enhancer of apoptotic cell death in a variety of cellular models. This effect is independent of its established cellular target, the mitochondrial benzodiazepine receptor (mBzR), since it is able to promote cell death also in mBzR knockout cells. Thus recently it was suggested that PK11195 might exert its effect by modulating the expression and function of the oncogene Bcl-2. We have previously demonstrated that Bcl-2 modulates cellular Ca2+ homeostasis as its overexpression reduces the Ca2+ concentration in the endoplasmic reticulum (ER) ([Ca2+](er)), impairing mitochondrial and cytosolic Ca2+ overload during cellular stress and therefore inhibiting the induction of the apoptotic cascade. Here, using ER, mitochondria and cytosolic targeted aequorin probes, we show that cellular treatment with PK11195 induces opposite changes in cellular Ca2+ homeostasis, increasing the [Ca2+](er) and amplifying IP(3) induced Ca2+ transients in mitochondria ([Ca2+](m)) and cytosol ([Ca2+](c)). This work provides evidence for a novel pharmacological effect of PK11195 on Ca2+ signalling which may be linked to its effect on Bcl-2 and account for its role in apoptotic cell death.
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PMID:Modulation of intracellular Ca2+ signalling in HeLa cells by the apoptotic cell death enhancer PK11195. 1892 43