Interaction of lutein with mitochondrial and artificial membranes

Addition of intact chloroplasts to mitochondria resulted in the uncoupling and inhibition of oxidative phosphorylation. The uncoupling principle was identified as the xanthophyll lutein. The oxidation of NADH was more sensitive to inhibition by lutein than was the oxidation of succinate or ascorbate. Xanthophyll stimulated the ATPase activity of mitochondria in the presence of $Mg^{2+}$; in the absence of $Mg^{2+}$, it inhibited the enzyme activity. Differential calorimetric scans revealed that incorporation of lutein into aq. dispersions of dipalmitoyl phosphatidyl choline decreased the transition enthalpy as well as the size of the cooperative unit, without change in the temp. of transition. Permeability of the bilayer to ascorbate and $Ca^{2+}$ was enhanced significantly in the presence of lutein. The efflux of $Ca^{2+}$ from mitochondria was enhanced. Incorporation of the xanthophyll broadened NMR peaks of both acyl side chain methylene and terminal Me protons without change in the line width of the choline head group Me proton signal. These results reveal that the deleterious action of lutein on mitochondrial oxidative phosphorylation results from its ability to integrate deep into the hydrophobic regions of the bilayer and perturb the microenvironment

Inhibition of mitochondrial electron transport and energy transduction by 2-methyl-4-dimethylaminoazobenzene in vitro

2-Methyl-4-dimethylaminoazobenzene (I) [54-88-6] inhibited electron transport and phosphorylation in tightly coupled rat liver mitochondria. It stimulated state 4 respiration, decreased ADP/O ratio, inhibited state 3 oxidation and abolished respiratory control. These effects reveal its action as an inhibitor uncoupler. Consistent with its preferential inhibition of the NADH-ubiquinone segment of the respiratory chain, ferricyanide reduction was far more sensitive to inhibition by I when NAD+-linked substrates were used as electron donors than when succinate was used. Like a true uncoupler, it stimulated the dormant ATPase [9000-83-3] activity in tightly coupled mitochondria in the presence and absence of Mg. However, in the absence of added Mg, dinitrophenol-stimulated activity was drastically inhibited indicating its action as a membrane destabilizing agent. In sonic submitochondrial particles, I inhibited energy-linked reverse electron transport and transhydrogenase reaction

Influence of clofibrate administration on the rate of synthesis of macromolecules in regenerating rat liver

Administration of the antihypercholesterolaemic drug clofibrate stimulates the rates of synthesis of nucleic acids and proteins in rat liver. The biosynthesis of mitochondrial proteins also is enhanced by the drug. In drug-fed animals, the rates of incorporation in vivo of radioactive precursors into DNA, RNA and proteins are stimulated even when the liver undergoes regeneration following partial hepatectomy. The rate of synthesis of mitochondrial proteins in the regenerative phase is higher in clofibrate-fed animals. These effects are consistent with the hepatomegalic and mitochondria-proliferating property of the drug

Effect of administration of clofibrate and clofenapate on kidney mitochondria of the rat

Abstract is not available

Effect of clofibrate on the adenosine triphosphatase activity of rat liver mitochondria

The antihypercholesterolemic drug clofibrate (ethyl-α-p-chlorophenoxyisobutyrate) stimulated the latent ATPase activity and “superstimulated” the uncoupler-induced ATPase activity of rat-liver mitochondria. Addition of clofibrate decreased the turbidity of mitochondrial suspensions and released considerable amount of mitochondrial protein into solution. In these properties it closely resembled detergents like Triton X-100 and deoxycholate. However, unlike the detergents, clofibrate required the presence of a permeant cation for its disruptive action. Also, it was without any such effect on sonic submitochondrial particles. The drug enhanced the uptake of both Mg2 and Cl− by mitochondria suggesting that osmotic swelling precedes lysis. Sonic submitochondrial particles prepared in the presence of clofibrate showed a greater yield and comparable ATPase activity

Interaction of lutein with phosphatidylcholine bilayers

The interaction of lutein, an inhibitory uncoupler of mitochondrial oxidative phosphorylation,with phospholipid liposome bilayers was examd. employing a variety of phys. methods.Differential calorimetric scans revealed that incorporation of lutein into aq. dispersions of dipalmitoylphosphatidylcholine broadened the main transition endotherm and decreased the transition enthalpy as well as the size of the cooperative unit without change in the temp. of transition.Permeability of the bilayer to ascorbate was enhanced significantly by the presence of lutein.The trapped vol. of the vesicles was decreased.Incorporation of lutein broadened the NMR peaks of both the acyl side-chain methylene and terminal Me protons without any change in the linewidth of the choline head-group Me proton signal.This indicated the ability of the compd. to integrate deep into the hydrophobic regions of the phospholipid bilayer distal to the polar regions.These results support earlier biochem. studies which revealed that the deleterious action of lutein on mitochondrial oxidative phosphorylation could be due to its ability to interact with membrane components and perturb the structure

Distribution of adriamycin in tissues and subcellular fractions

Substantial amounts of adriamycin [23214-92-8] were recovered in various organs after i.p. administration in rats. The highest concenration of the drug was found in the kidneys. Subcellularly, in heart, liver, and kidney, the nuclear fraction contained the highest concentration of the drug, an observation consistent with the finding that adriamycin shows greater affinity for the nuclear fraction when added to tissue homogenates in vitro. These results are discussed in relation to the cardiotoxicity of adriamycin. Procedures for improving the fluorometric method for the detection of adriamycin are also given

Effect of administration of diethylhexyl phthalate on the function and turnover of rat hepatic mitochondria

Administration of the widely used plasticizer di(2-ethyihexyl)phthalate (2% w/w) in the diet to the rat caused proliferation of mitochondria in the liver. The number of mitochondria as well as the amount of protein recovered in the organellar fraction was doubled. Mitochondria isolated from the livers of treated animals showed decreased (50%) respiratory activity. The content and activity of cytochrome oxidase were also decreased. The specific incorporation of amino acids into the proteins of whole liver and of mitochondria was not increased in plasticizer-treated animals. Isolated mitochondria also did not show any difference in the rate of incorporation of amino acids into proteins. The half-lives of whole liver proteins and of mitochondria were increased in plasticizer-fed animals. The half-life of cytochrome oxidase, however, was unaffected by the treatment. The pattern of double labeling of mitochondrial proteins confirmed decreased turnover in plasticizer-treated animals