Biomedical subjects

V G Zgoda

Publications and source records attributed to V G Zgoda.

5 recordsLinked to original sources

PubMed2026

The influence of neuroprotector isatin on haloperidolinduced catalepsy and proteomic profile of mice brain.

Isatin (indol-2,3-dione) is an endogenous regulator found in humans and animals. It interacts with numerous target proteins and exhibits a wide range of biological activities, including neuroprotective action in animal models of Parkinson's disease (PD) induced by administration of neurotoxins MPTP (1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine) or rotenone. An antipsychotic drug haloperidol, which impairs neurotransmitter balance in the nigrostriatal pathway, models dopamine deficiency and promotes the development of motor disorders characteristic of PD. In this work, the effect of two doses of isatin (10 mg/kg and 80 mg/kg) on the haloperidol catalepsy and on the proteomic profile of mice brain was investigated. The pretreatment of animals with isatin (1 h before haloperidol administration) reduced the occurrence of haloperidol catalepsy. The administration of haloperidol and also isatin with haloperidol influenced the relative content of a number of proteins associated with PD and other neurodegenerative diseases.

Animals↗

PubMed1999

Heme and apoprotein modification of cytochrome P450 2B4 during its oxidative inactivation in monooxygenase reconstituted system.

The mechanism of the cytochrome P450 2B4 modification by hydrogen peroxide (H2O2) formed as a result of partial coupling of NADPH-dependent monooxygenase reactions has been studied in the monooxygenase system reconstituted from the highly purified microsomal proteins: cytochrome P450 2B4 (P450) and NADPH-cytochrome P450 reductase in the presence of detergent Emulgen 913. It was found, that H2O2-mediated P450 self-inactivation during benzphetamine oxidation is accompanied by heme degradation and apoenzyme modification. The P450 heme modification involves the heme release from the enzyme under the action of H2O2 formed within P450s active center via the peroxycomplex decay. Additionally, the heme lost is destroyed by H2O2 localized outside of enzyme's active center. The modification of P450 apoenzyme includes protein aggregation that may be due to the change in the physico-chemical properties of the inactivated enzyme. The modified P450 changes the surface charge that is confirmed by the increasing retention time on the DEAE column. Oxidation of amino acid residues (at least cysteine) may lead to the alteration into the protein hydrophobicity. The appearance of the additional ionic and hydrophobic attractions may lead to the increase of the protein aggregation. Hydrogen peroxide can initiate formation of crosslinked P450 dimers, trimers, and even polymers, but the main role in this process plays nonspecific radical reactions. Evidence for the involvement of hydroxyl radical into the P450 crosslinking is carbonyl groups formation.

Animals↗

PubMedDate not supplied

[Modification of cytochrome P-450 apoenzyme during its oxidative self-inactivation in a reconstituted mono-oxygenase system].

The hemoprotein self-inactivation is accompanied by oxidation of all-groups, carbonyl group formation, changes in aggregate state and apoenzyme polymerization. It is probable that heme loss and oxidative modification of apoenzyme is a important step in regulation of P450 decay in cell.

Apoenzymes↗

PubMedDate not supplied

[Self-inactivation of cytochrome P-450 2B4 during catalytic cycle in the monooxygenase reconstituted system].

The mechanism of cytochrome P450 2B4 self-inactivation during catalytic turnover has been studied in monooxygenase reconstituted system containing from monomers of the membrane proteins: NADPH-cytochrome P450 reductase, cytochrome P450 2B4 and cytochrome b5 in presence of detergent emulgen 913. It was shown that P450 is inactivated at a high rate during benzphetamine oxidation. Hydrogen peroxide formed at the cytochrome P450 active center plays the key role in hemoprotein inactivation during uncoupling of monooxygenase reactions. The mechanism oxidative heme modification has been studied in monooxygenase reconstituted system also. It was demonstrated that formed at the active center is responsible for the loss of P450 heme and localized outside of active hemoprotein center is responsible for the heme destruction.

Aryl Hydrocarbon Hydroxylases↗

PubMedDate not supplied

[Oxidative modification of cytochrome P450 and other macromolecules during its turnover].

Possible mechanisms of cytochrome P4502B4 modification by H2O2 formed during catalytic turnover have been studied. Oxidative self-inactivation of cytochrome P4502B4 in monooxygenase system, reconstituted from highly purified membrane proteins: cytochrome P4502B4, NADDPH-cytochrome P450 reductase and cytochrome b5 in the presence of detergent Emulgen 913, involves the heme destruction and apoenzyme modification. The cytochrome P450 self-inactivation is accompanied by protein aggregation, oxidation of SH-groups and changes of the surface charge. H2O2 and non-specific radical reactions may be responsible for the intermolecular cross-linking. Oxidative modification of cytochrome P4502B4 may be initial stage of the protein decay in the cell.

Cytochrome P-450 Enzyme System↗