81 research outputs found
A STUDY OF THE SORPTION CAPACITY OF LECITHIN MODIFIED NATURAL SORBENT RELATIVE TO NATIVE PROTEIN
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Cytotoxic and genotoxic effects of Br-containing oxaphosphole on Allium cepa L. root tip cells and mouse bone marrow cells
The continuous production and release of chemicals into the environment has led to the need to assess their genotoxicity. Numerous organophosphorus compounds with different structures have been synthesized in recent years, and several oxaphosphole derivatives are known to possess biological activity. Such chemical compounds may influence proliferating cells and cause disturbances of the genetic material. In this study, we examined the cytotoxicity and genotoxicity of 4-bromo-N,N-diethyl-5,5-dimethyl-2,5-dihydro-1,2-oxaphosphol-2-amine 2-oxide (Br-oxph). In A. cepa cells, Br-oxph (10-9 M, 10 -6 M and 10 -3 M) reduced the mitotic index 48 h after treatment with the two highest concentrations, with no significant effect at earlier intervals. Mitotic cells showed abnormalities 24 h and 48 h after treatment with the two lowest concentrations but there were no consistent changes in interphase cells. Bone marrow cells from mice treated with Br-oxph (2.82 x 10 -3 ÎŒg/kg) also showed a reduced mitotic index after 48 h and a greater percentage of cells with aberrations (principally chromatid and isochromatid breaks). These findings indicate the cytotoxicity and genotoxicity of Br-oxph in the two systems studied
Characterisation of the Cullin-3 mutation that causes a severe form of familial hypertension and hyperkalaemia
Deletion of exon 9 from Cullinâ3 (CUL3, residues 403â459: CUL3Î403â459) causes pseudohypoaldosteronism type IIE (PHA2E), a severe form of familial hyperkalaemia and hypertension (FHHt). CUL3 binds the RING protein RBX1 and various substrate adaptors to form CullinâRINGâubiquitinâligase complexes. Bound to KLHL3, CUL3âRBX1 ubiquitylates WNK kinases, promoting their ubiquitinâmediated proteasomal degradation. Since WNK kinases activate Na/Cl coâtransporters to promote salt retention, CUL3 regulates blood pressure. Mutations in both KLHL3 and WNK kinases cause PHA2 by disrupting CullinâRINGâligase formation. We report here that the PHA2E mutant, CUL3Î403â459, is severely compromised in its ability to ubiquitylate WNKs, possibly due to altered structural flexibility. Instead, CUL3Î403â459 autoâubiquitylates and loses interaction with two important Cullin regulators: the COP9âsignalosome and CAND1. A novel knockâin mouse model of CUL3WT/Î403â459 closely recapitulates the human PHA2E phenotype. These mice also show changes in the arterial pulse waveform, suggesting a vascular contribution to their hypertension not reported in previous FHHt models. These findings may explain the severity of the FHHt phenotype caused by CUL3 mutations compared to those reported in KLHL3 or WNK kinases
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