Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.5.3 (complex I)
 8,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The specific activities of the succinate dehydrogenase-coenzyme Q reductase were determined in mitochondria from the thymus and the spleen of aged mice (20, 22 and 24 months) as compared with young mice (10 weeks). Significant steep escalation of the deficiency of coenzyme Q-enzyme activity was observed in the thymus of all three groups of aged mice. No significant deficiency was found in the mitochondria of the spleen. The ratios between the liver weight:body weight and the spleen weight:body weight in young and aged mice are practically unchanged, but the thymus weight:body weight ratio decreases significantly in all three groups of aged mice. The described age-dependent anatomical and functional alterations in the thymus most likely form the base for the development of the T cell determined suppression of the immunological responsiveness, present in aged mice.
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PMID:Coenzyme Q deficiency in aged mice. 28 77

Chromomycin A3 is an antitumor antibiotic which blocks macromolecular synthesis via reversible interaction with DNA template only in the presence of divalent metal ions such as Mg2+. The role of Mg2+ in this antibiotic-DNA interaction is not well understood. We approached the problem in two steps via studies on the interaction of (i) chromomycin A3 and Mg2+ and (ii) chromomycin A3-Mg2+ complex(es) and DNA. Spectroscopic techniques such as absorption, fluorescence, and CD were employed for this purpose. The results could be summed up in two parts. Absorption, fluorescence, and CD spectra of the antibiotic change upon addition of Mg2+ due to complex formation between them. Analysis of the quantitative dependence of change in absorbance of chromomycin A3 (at 440 nm) upon input concentration of Mg2+ indicates formation of two types of complexes with different stoichiometries and formation constants. Trends in change of fluorescence and CD spectroscopic features of the antibiotic in the presence of Mg2+ at different concentrations further corroborate this result. The two complexes are referred to as complex I (with 1:1 stoichiometry in terms of chromomycin A3:Mg2+) and complex II (with 2:1 stoichiometry in terms of chromomycin A3:Mg2+), respectively, in future discussions. The interactions of these complexes with calf thymus DNA were examined to check whether they bind differently to the same DNA. Evaluation of binding parameters, intrinsic binding constants, and binding stoichiometry, by means of spectrophotometric and fluorescence titrations, shows that they are different. Distinctive spectroscopic features of complexes I and II, when they are bound to DNA, also support that they bind differently to the above DNA. Measurement of thermodynamic parameters characterizing their interactions with calf thymus DNA shows that complex I-DNA interaction is exothermic, in contrast to complex II-DNA interaction, which is endothermic. This feature implies a difference in the molecular nature of the interactions between the complexes and calf thymus DNA. These observations are novel and significant to understand the antitumor property of the antibiotic. They are also discussed to provide explanations for the earlier reports that in some cases appeared to be contradictory.
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PMID:Role of magnesium ion in the interaction between chromomycin A3 and DNA: binding of chromomycin A3-Mg2+ complexes with DNA. 155 Aug 24

The bactericidal activity of Tinopal AN [1,1-bis(3,N-5-dimethyl-benzoxazol-2-yl)-methine p-toluene sulphonate] was shown to be due to a mechanism entirely independent of its inhibitory effects upon NADH dehydrogenase which were reported previously. Whereas the compound had no significant effect upon DNA synthesis in Escherichia coli D22, RNA and protein synthesis were immediately and markedly inhibited. In confirmation, Tinopal AN caused an immediate cessation in inducible beta-galactosidase synthesis in the same organism. An in vitro assay of the transcription of calf-thymus DNA by purified E. coli RNA polymerase showed that this process was inhibited by Tinopal AN.
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PMID:The antibacterial action of Tinopal AN. 620

Mithramycin is an anticancer drug that blocks macromolecular synthesis via reversible interaction with the DNA template in the presence of bivalent metal ions such as Mg2+. The role of Mg2+ in this antibiotic-DNA interaction is not clear. We approached the problem in two steps via studies on the interactions between (i) mithramycin and Mg2+ and (ii) mithramycin-Mg2+ complex(es) and DNA. Spectroscopic techniques such as absorption, fluorescence, and CD were employed for the purpose. From equilibrium and kinetic studies, we earlier reported that MTR forms two different types of complexes with Mg2+ [Aich, P., & Dasgupta, D. (1990) Biochem. Biophys. Res. Commun. 173, 689]. The two complexes are referred to as complex I (with 1:1 stoichiometry in terms of mithramycin: Mg2+) and complex II (with 2:1 stoichiometry in terms of mithramycin: Mg2+). In this report, we have further characterized these complexes by fluorescence spectroscopy. Interactions of these complexes with calf thymus DNA were examined to elucidate their binding. Evaluation of binding parameters (intrinsic binding constant and stoichiometry) from spectrophotometric and fluorimetric titrations suggests that the complexes bind differently to the same DNA. Measurement of van't Hoff enthalpies for the interaction of the two ligands and DNA shows that the complex I-DNA interaction is exothermic, in contrast to the endothermic nature of the complex II-DNA interaction. This could originate from a difference in the molecular nature of the interactions between the complexes and calf thymus DNA. Our studies to detect the nature of the groove via which these complexes bind to DNA suggest that both complexes approach via the minor groove of the DNA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of magnesium ion in mithramycin-DNA interaction: binding of mithramycin-Mg2+ complexes with DNA. 782 85

The membranotropic properties of block co-polymers and their protein conjugates were studied by their effect on the rate of oxygen consumption by isolated liver mitochondria and on thymus-derived lymphocytes. The block co-polymers consisted of poly(ethylene oxide) (PoE) [poly(ethylene glycol)] and poly(propylene oxide) (PoP) to give either PoE-PoP or PoE-PoP-PoE. Both types inhibited uncoupled respiration of liver mitochondria in a medium containing glutamate and malate and also of lymphocytes. They also uncoupled respiration in the presence of succinate in K(+)-containing medium and of lymphocytes. A method is described for linking protein to the block polymers to form conjugates. Such conjugates were formed from alpha-chymotrypsin, BSA and cytochrome c, all of which produced similar effects on the respiration of the isolated mitochondria and lymphocytes. The data suggest that both the block co-polymers and their protein conjugates inhibit the NADH dehydrogenase complex and induce a K(+)-conductivity of the mitochondrial inner membrane; the surface activity of the conjugates allows them to pass through the plasma membrane and interact with the mitochondrial inner membrane.
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PMID:The influence of pluronics and their conjugates with proteins on the rate of oxygen consumption by liver mitochondria and thymus lymphocytes. 829 10

Di-n-butyltin dichloride (DBTC) and tri-n-butyltin chloride (TBTC) cause thymus atrophy in rodents. At low doses, antiproliferative modes of action have been shown to be involved, whereas at higher doses apoptosis seems to be the mechanism of thymotoxicity by these chemicals. In vitro, a similar concentration-dependency has been observed. The purpose of the present research was to investigate the mechanisms underlying DNA fragmentation induced by these organotin compounds in freshly isolated rat thymocytes. As previously shown for TBTC, DBTC is also able to significantly increase intracellular Ca(2+) level ([Ca(2+)](i)). The rise in [Ca(2+)](i), already evident 5 min after treatment, was followed by a dose- and time-dependent generation of reactive oxygen species (ROS) at the mitochondrial level. Simultaneously, organotins induced the release of cytochrome c from the mitochondrial membrane into the cytosol. ROS production and the release of cytochrome c were reduced by BAPTA, an intracellular Ca(2+) chelator, or rotenone, an inhibitor of the electron entry from complex I to ubiquinone, indicating the important role of Ca(2+) and mitochondria during these early intracellular events. Furthermore, we demonstrated that rotenone prevents apoptosis induced by 3 microM DBTC or TBTC and, in addition, that both BAPTA and Z-DEVD FMK (mainly a caspase-3 inhibitor) decreased apoptosis by DBTC (already shown for TBTC). Taken together these data show the apoptotic pathway followed by organotin compounds starts with an increase of [Ca(2+)](i), then continues with release of ROS and cytochrome c from mitochondria, activation of caspases, and finally results in DNA fragmentation.
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PMID:Organotins induce apoptosis by disturbance of [Ca(2+)](i) and mitochondrial activity, causing oxidative stress and activation of caspases in rat thymocytes. 1109 71