Lipoxygenases (LOX) constitute a heterogeneous family of lipid peroxidizing enzymes which catalyze the stereospecific insertion of molecular oxygen into polyunsaturated fatty acids. The primary products of LOX reaction are hydroperoxy fatty acids, which are rapidly reduced to the corresponding hydroxy derivatives. In mammalian organisms, there are 4 main LOX isoforms, 5-LOX, 8-LOX, 12-LOX, 15-LOX, constituting hydroperoxides with positional and stereo specificity. In the subsequent metabolic processes they provide significant cell signaling molecules and secondary messengers taking part in the development of inflammatory, tumorous and other diseases. Recent studies clarified the role of lipoxygenases in various diseases. The study of the structure and the active site of enzyme, preparation of recombinant forms with the targeted gene mutations have shown possibilities for better understanding the lipoxygenase role in various pathological processes. Searching for selective inhibitors of LOX isoenzymes is an active area of investigation. They can represent an important research tool or become a promising targeted therapy of a wide range of human diseases.
- MeSH
- Isoenzymes genetics classification MeSH
- Arachidonic Acid metabolism MeSH
- Humans MeSH
- Lipoxygenases * pharmacology chemistry classification MeSH
- Molecular Conformation MeSH
- Mutation MeSH
- Fatty Acids, Unsaturated metabolism MeSH
- Mammals MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Keywords
- lyzyl oxidáza,
- MeSH
- Histones biosynthesis MeSH
- Immunohistochemistry methods utilization MeSH
- Isoenzymes classification adverse effects MeSH
- Keratoconus * etiology pathology MeSH
- Rabbits MeSH
- Humans MeSH
- Antibodies, Monoclonal, Murine-Derived MeSH
- Mice MeSH
- Prospective Studies MeSH
- Cornea physiology MeSH
- Oxygen Compounds * adverse effects MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
The effect of protein kinase C (PKC) inhibitors on porcine oocyte activation by calcium ionophore A23187 was studied. Calcium ionophore applied in a 50 microM concentration for 10 min induced activation in 74% of oocytes matured in vitro. When the ionophore-treated oocytes were exposed to the effect of bisindolylmaleimide I, which inhibits calcium-dependent PKC isotypes (PKC-alpha, -beta(I), -beta(II), -gamma,) and calcium-independent PKC isotypes (PKC-delta, -epsilon), the portion of activated oocytes decreased (at a concentration of 100 nM, 2% of the oocytes were activated). Go6976, the inhibitor of calcium-dependent PKC isotypes PKC-alpha, -beta(I) did not prevent the action of the oocytes treated with calcium ionophore in concentrations from 1 to 100 microM. The inhibitor of PKC-beta(I) and beta(II) isotypes, hispidin, in a concentration of 2 microM-2 mM, was not effective either. The inhibitor of PKC-delta isotype, rottlerin, suppressed activation of the oocytes by calcium ionophore (no oocyte was activated at 10 microM concentration). The PKC-delta isotype in matured porcine oocytes, studied by Western blot analysis, appeared as non-truncated PKC-delta of 77.5 kDa molecular weight, on the one hand, and as truncated PKC-delta, which was present in the form of a doublet of approximately 62.5 and 68 kDa molecular weight, on the other hand. On the basis of these results, it can be supposed that PKC participates in the regulation of processes associated with oocyte activation. Calcium-dependent PKC-alpha, -beta isotypes do not seem to play any significant role in calcium activation. The activation seems to depend on the activity of the calcium-independent PKC-delta isoform.
- MeSH
- Acetophenones pharmacology MeSH
- Benzopyrans pharmacology MeSH
- Calcimycin pharmacology MeSH
- Indoles pharmacology MeSH
- Protein Kinase Inhibitors pharmacology MeSH
- Ionophores pharmacology MeSH
- Isoenzymes antagonists & inhibitors physiology classification MeSH
- Carbazoles pharmacology MeSH
- Maleimides pharmacology MeSH
- Oocytes physiology drug effects MeSH
- Swine physiology MeSH
- Protein Kinase C antagonists & inhibitors physiology classification MeSH
- Pyrones pharmacology MeSH
- Calcium physiology MeSH
- Blotting, Western MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Case Reports MeSH
- MeSH
- Flavins MeSH
- Isoenzymes analysis classification MeSH
- Oxygenases physiology adverse effects MeSH
- Substrate Specificity MeSH
- Xenobiotics metabolism toxicity MeSH
- Publication type
- Review MeSH
