ABSTRACT
AIM: To estimate the combined action of C60 fullerene and light irradiation on viability of L1210 leukemic cells, nitric oxide (NO) generation, p38 mitogen-activated protein kinase (MAPK) activity and cell cycle distribution. METHODS: Cell viability was assessed by MTT test. Light-emitting diode lamp (λ = 410-700 nm, 2.45 J/cm(2) ) was used for C60 fullerene photoexcitation. Nitrite level and NO-synthase activity were measured by Griess reaction and by conversion of L-arginine to L-citrulline, respectively. p38 MAPK activity was assessed by Western blot analysis. Cell cycle distribution was determined by flow cytometry. RESULTS: It was shown that light irradiation of C60 fullerene-treated L1210 cells was accompanied by 55% decrease of their viability at 48 h of culture. Nitrite level measured as an index of reactive NO generation was increased at the early period after C60 fullerene photoexcitation due to activation of both constitutive and inducible NO-synthase isoforms. The simultaneous activation of p38 MAPK was detected. Accumulation of L1210 cells in sub-G1 phase of cell cycle was observed after C60 fullerene photoexcitation. CONCLUSION: Photoexcited C60 fullerene exerts cytotoxic effect, at least in part, through triggering production of reactive NO species and activation of p38 kinase apoptotic pathways in L1210 leukemic cells.
Subject(s)
Antineoplastic Agents/pharmacology , Cell Survival/drug effects , Fullerenes/pharmacology , Leukemia/drug therapy , Nitric Oxide/metabolism , Photosensitizing Agents/pharmacology , p38 Mitogen-Activated Protein Kinases/metabolism , Animals , Cell Cycle/drug effects , Enzyme Activation/drug effects , Leukemia/metabolism , Mice , Nitric Oxide Synthase Type II/metabolism , Ultraviolet RaysABSTRACT
The changes of functional state isolated by Lanhendorf old rat hearts with low content of ubiqinone--coenzyme Q (CoQ) under activation of it endogenous synthesis through administration of precursors--4-hydroxybenzoic acid, methionine and modulator vitamin E were studied. The activation of ubiqinone biosynthesis contribute to cardioprotective effect due to reduce the degree of the ischemia-reperfusion injury in old rat heart, namely the restoration of myocardial contractile function and coronary flow as well as decrease the end diastolic pressure and oxygen cost of the heart compared with control group of the animals during ischemia-reperfusion. Thus the results allow to conclude that the activation of KoQ biosynthesis under administration of it precursors has protective effect in the development of the heart postreperfusion damages in aging.
Subject(s)
Aging/metabolism , Myocardial Reperfusion Injury/prevention & control , Myocardium/metabolism , Ubiquinone/biosynthesis , Aging/drug effects , Aging/pathology , Animals , Cardiotonic Agents/pharmacology , Coronary Circulation/drug effects , Heart/drug effects , Heart Function Tests , In Vitro Techniques , Male , Methionine/pharmacology , Myocardial Reperfusion , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/pathology , Myocardium/pathology , Parabens/pharmacology , Rats , Rats, Wistar , Ubiquinone/physiology , alpha-Tocopherol/pharmacologyABSTRACT
This research work is devoted to study of the sensitivity of mitochondrial permeability transition pore (MPTP) opening to its inductors--ions Ca2+ (10(-4) mol/l) and oxidant phenylarsine oxide (10(-4) mol/l) and content of ubiquinone (coenzyme Q, CoQ) and vitamin E in heart mitochondria of adult, old (control) and old rats under administration of precursors an modulator of CoQ biosynthesis--4-hydroxybenzoic acid, methionine and modulator of CoQ biosynthesis, namely vitamin E. The results of our research demonstrate that administration of complex of biologically active substances, which are precursors and modulators of CoQ biosynthesis, leads to decrease in the sensitivity of MPTP opening to its inductors and increase of CoQ and vitamin E content in old rats heart mitochondria. Therefore the results obtained lead to a conclusion that increase of CoQ content due to administration of precursors and modulator of its biosynthesis is an effective way in the inhibition of MPTP opening. This approach as well as application of CoQ-containing medicals may be used for correction of mitochondrial dysfunction under various pathologies of cardiovascular system and in aging.
Subject(s)
Aging/metabolism , Mitochondria, Heart , Mitochondrial Membrane Transport Proteins/metabolism , Myocardium/metabolism , Ubiquinone/biosynthesis , Aging/drug effects , Animals , Arsenicals/pharmacology , Calcium/pharmacology , Male , Methionine/pharmacology , Mitochondria, Heart/drug effects , Mitochondria, Heart/metabolism , Mitochondrial Membrane Transport Proteins/antagonists & inhibitors , Mitochondrial Permeability Transition Pore , Mitochondrial Swelling/drug effects , Parabens/pharmacology , Rats , Rats, Wistar , Vitamin E/metabolism , Vitamin E/pharmacologyABSTRACT
The paper is dedicated to the study of peculiarities of ubiquinone and ubichromenol distribution and metabolism in subcellular fractions of rats' liver under A,E-hypovitaminosis. It is shown, that dietary deprivation of vitamins A and E leads to a sharp decrease in intensity of CoQ biosynthesis in rats' liver tissue and to its intracellular redistribution. Under these circumstances the observed decrease in the inclusion of labelled tyrosine in rats' liver CoQ under A,E-hypovitaminosis may be really caused by dietary deprivation of vitamin E.
Subject(s)
Chromans/metabolism , Liver/metabolism , Ubiquinone/metabolism , Vitamin A Deficiency/metabolism , Vitamin E Deficiency/metabolism , Animals , Rats , Tocopherols/administration & dosage , Tritium , Tyrosine/chemistry , Ubiquinone/biosynthesis , Vitamin A/administration & dosage , Vitamin A Deficiency/complications , Vitamin E Deficiency/complicationsABSTRACT
In addition to well known function of ubiquinone as a component of mitochondrial electron-transport chain and antioxidant, the latest research data that evidence for its function as a regulator of the processes connected with gene expression, signal transduction, including regulation of apoptosis are considered in this review. We also discuss practical aspects of use of ubiquinone for prophylaxis and treatment of cardiovascular, oncological diseases, pathologies of immune system, disorders caused by the effect of ionizing radiation.
