The cardiovascular effects of vitamin C (VitC) could be mediated by epoxyeicosatrienoic acids (EETs). We aimed to study the mechanism of VitC-dependent microsomal formation of cis- and trans-EETs and the regulation of...The cardiovascular effects of vitamin C (VitC) could be mediated by epoxyeicosatrienoic acids (EETs). We aimed to study the mechanism of VitC-dependent microsomal formation of cis- and trans-EETs and the regulation of EET levels in rat isolated perfused kidneys and in vivo. VitC biphasically stimulated rat kidney microsomal cis- and trans-EET formation in a ratio of 1:2, involving the participation of lipid hydroperoxides (LOOHs), Fe2+ , and cytochrome P450 (CYP). Levels of LOOHs correlated with microsomal EET production. LOOH stimulation of CYP isoforms resulted in preferred trans- over cis-EET formation from arachidonic acid and was associated with the cleavage of LOOHs, which indicated a CYP peroxy-genase activity. EETs contributed to VitC-induced vasodilator responses in rat isolated perfused kidneys. VitC (1 mg/ml) given in the drinking water for 9 days doubled rat urinary EET excretion, increased plasma levels of EETs, mostly trans-EETs, by 40%, and reduced plasma levels of 20-hydroxyeicosatetraenoic acid. Depletion of VitC in brain cortex and kidney tissues by more than 20- and 50-fold, respectively, in gulonolactone oxidase-knockout mice was associated with mild increases in tissue EETs. These data suggest that LOOHs are a determinant factor for EET formation in vivo in which VitC exerts a key regulatory effect. VitC-activated CYP peroxygenase activity may represent a CYP interaction with lipoxygenases and cyclooxygenases to mediate the cardiovascular effects of VitC via formation of EETs.展开更多
Cilia and flagella are organelles of motility that enable cells to swim or move liquid over its surface. An exhaustive literature survey for the presence of the organelle in organisms across phyla showed that most ani...Cilia and flagella are organelles of motility that enable cells to swim or move liquid over its surface. An exhaustive literature survey for the presence of the organelle in organisms across phyla showed that most animal cells harbor cilia in contrast to very few fungal cells. While this was not unexpected, it was the position and arrangement of this organelle in each cell that intrigued our attention. Natural selection might have favored motility over chemotaxis;and it would have done so to evolve a stable structure that could have undergone an optimization process requiring a precise geometry in the shape of cells and the structure that would help cells to move. The positioning of such a structure would play a pre-dominant role in optimal motility. It is now known that the flagellar position of a cell is a genetically distinct trait, occasionally used in phylogeny of bacteria, distributed in distinguishing patterns over cellular surface, but basically are of two types, either polar (one flagellum arising from one pole per cell) or peritrichous (lateral flagella distributed over the entire cell surface). Irrespective of the cellular habitat, flagella origin, ultrastructure and proteome, the present investigation surveyed 26 sub-types of flagellar arrangements from as many species as possible. A peculiar pattern ensued-Prokaryotes harbored predominantly polar and peritrichous types;eukaryotes showed a mere change of the peritrichous one. These numbers when used to create a Similarity tree depicted a similarity distance of 14 between the Eubacteria and Archaebacteria forming the first neighborhood;Protozoans, Algae, Fungi, Plantae and Animalia formed a second neighborhood. We offer a working hypothesis for this pattern and the gradual shift in the flagellar arrangement from polar, peritrichous, sub-apical, and apical to lateral throughout evolution.展开更多
文摘The cardiovascular effects of vitamin C (VitC) could be mediated by epoxyeicosatrienoic acids (EETs). We aimed to study the mechanism of VitC-dependent microsomal formation of cis- and trans-EETs and the regulation of EET levels in rat isolated perfused kidneys and in vivo. VitC biphasically stimulated rat kidney microsomal cis- and trans-EET formation in a ratio of 1:2, involving the participation of lipid hydroperoxides (LOOHs), Fe2+ , and cytochrome P450 (CYP). Levels of LOOHs correlated with microsomal EET production. LOOH stimulation of CYP isoforms resulted in preferred trans- over cis-EET formation from arachidonic acid and was associated with the cleavage of LOOHs, which indicated a CYP peroxy-genase activity. EETs contributed to VitC-induced vasodilator responses in rat isolated perfused kidneys. VitC (1 mg/ml) given in the drinking water for 9 days doubled rat urinary EET excretion, increased plasma levels of EETs, mostly trans-EETs, by 40%, and reduced plasma levels of 20-hydroxyeicosatetraenoic acid. Depletion of VitC in brain cortex and kidney tissues by more than 20- and 50-fold, respectively, in gulonolactone oxidase-knockout mice was associated with mild increases in tissue EETs. These data suggest that LOOHs are a determinant factor for EET formation in vivo in which VitC exerts a key regulatory effect. VitC-activated CYP peroxygenase activity may represent a CYP interaction with lipoxygenases and cyclooxygenases to mediate the cardiovascular effects of VitC via formation of EETs.
文摘Cilia and flagella are organelles of motility that enable cells to swim or move liquid over its surface. An exhaustive literature survey for the presence of the organelle in organisms across phyla showed that most animal cells harbor cilia in contrast to very few fungal cells. While this was not unexpected, it was the position and arrangement of this organelle in each cell that intrigued our attention. Natural selection might have favored motility over chemotaxis;and it would have done so to evolve a stable structure that could have undergone an optimization process requiring a precise geometry in the shape of cells and the structure that would help cells to move. The positioning of such a structure would play a pre-dominant role in optimal motility. It is now known that the flagellar position of a cell is a genetically distinct trait, occasionally used in phylogeny of bacteria, distributed in distinguishing patterns over cellular surface, but basically are of two types, either polar (one flagellum arising from one pole per cell) or peritrichous (lateral flagella distributed over the entire cell surface). Irrespective of the cellular habitat, flagella origin, ultrastructure and proteome, the present investigation surveyed 26 sub-types of flagellar arrangements from as many species as possible. A peculiar pattern ensued-Prokaryotes harbored predominantly polar and peritrichous types;eukaryotes showed a mere change of the peritrichous one. These numbers when used to create a Similarity tree depicted a similarity distance of 14 between the Eubacteria and Archaebacteria forming the first neighborhood;Protozoans, Algae, Fungi, Plantae and Animalia formed a second neighborhood. We offer a working hypothesis for this pattern and the gradual shift in the flagellar arrangement from polar, peritrichous, sub-apical, and apical to lateral throughout evolution.
