Kinase Assay: |
Hereditas. 2011 Nov;148(4-5):118-24. | Dl-α-tocopherol enhances the herbicide 1,1'-dimetyl-4,4'-bipyridium dichloride (paraquat, PQ) genotoxicity in cultured anuran leukocytes.[Pubmed: 22150823] | METHODS AND RESULTS: This cytogenetic and pharmacological study attempts to clarify genotoxicity-enhancement-effect of DL-alpha-Tocopherol (one form of vitamin E) in combination with the herbicide 1,1'-dimetyl-4,4'-bipyridium dichloride (paraquat, PQ) on cultured anuran leukocytes using the superoxide dismutase-mimic Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin (Mn(III)TMpyP), the hydrogen peroxide-scavenger catalase and the electron donor nicotinamide adenine dinucleotido phosphate (NADPH).DL-alpha-Tocopherol only did not induce any structural chromosomal damage in the leukocytes. PQ plus DL-alpha-Tocopherol, however, enhanced the genotoxic effect of PQ. Furthermore, PQ plus DL-alpha-Tocopherol-enhanced chromosomal damage was also inhibited by Mn(III)TMpyP plus catalase. CONCLUSIONS: These results suggest that DL-alpha-Tocopherol in combination with PQ functions as an electron donor to PQ. | J Cell Physiol. 1997 Sep;172(3):351-60. | dl-alpha-tocopherol, a potent inhibitor of phorbol ester induced shape change of erythro- and megakaryoblastic leukemia cells.[Pubmed: 9284955] | Synthetic vitamin E, DL-alpha-Tocopherol, added to a human erythroleukemia HEL and a megakaryoblastic leukemia, Meg-01, cell culture produced potent dose-dependent inhibition of phorbol ester-induced adhesion and of the morphologic changes accompanying it. METHODS AND RESULTS: The inhibition was reversible by withdrawal of supplemental vitamin E from the medium. DL-alpha-Tocopherol also inhibited protein kinase C activity both at baseline and after phorbol ester stimulation. Arachidonic acid stimulated protein kinase C activity of erythroleukemia cells and promoted their adhesion, an effect that was also inhibited by DL-alpha-Tocopherol. Introduction of a protein kinase C-neutralizing antibody or a protein kinase C-inhibitor substrate into permeabilized HEL cells inhibited phorbol ester-induced adhesion and shape change. DL-alpha-Tocopherol also affected the cellular distribution of protein kinase C, shifting the major portion of the enzyme to the cytosol fraction and reducing phorbol ester-induced membrane association of the enzyme. CONCLUSIONS: Thus, protein kinase C appears to mediate shape change and adhesion, both of which are strongly inhibited by DL-alpha-Tocopherol. |
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