RESUMEN
The lipid peroxidation (LPO) level between in the adult and old rats brain and liver was determined as to be essentially undiffering. Stress activated the LPO independence the age of animals and tissues investigated. The concentration changes of LPO products testify to it. In the adult rats under the stress capability of tissues to induction in vitro ferment and ascorbat-depending LPO, in comparison with the control, decreases, at old--does not change in the brain and considerably grows in the liver. Stress is accompanied by an oppression of Na, K-ATP-ase PM activity of hepatocytes, more expressed in the old animals.
Asunto(s)
Envejecimiento/metabolismo , Encéfalo/metabolismo , Peroxidación de Lípido , Estrés Fisiológico/metabolismo , Animales , Masculino , Ratas , Ratas WistarRESUMEN
Studies were made of the effects of various classes of lipoproteins (LP) from the blood of rabbits with experimental hypercholesterolemia and human subjects with pronounced atherosclerosis on the vascular tone of rat thoracic aorta specimens. In hypercholesterolemia, there was a considerable weakening of a vasodilatory action of atherogenic LP fractions--LDL and VLDL. A vasodilatory effect of HDLP was not changed. In subjects suffering from atherosclerosis vasodilatory effects of both atherogenic and antiatherogenic HDLP decreased significantly. The revealed changes were related to shifts in lipid and protein components of LP complexes manifesting in the development of dyslipoproteinemia and dysapoproteinemia. In atherosclerosis accompanied with more profound changes suppression of vasodilatory effects of LP is greater than in transient experimental hypercholesterolemia. Consequently, changes of lipid and apo composition of LP and weakening of their vasodilatory action play a considerable role in the vessel tone changes in atherogenic situation.
Asunto(s)
Apolipoproteínas/farmacología , Arteriosclerosis/sangre , Hipercolesterolemia/sangre , Lipoproteínas/farmacología , Vasoconstrictores/farmacología , Vasodilatadores/farmacología , Anciano , Animales , Aorta Torácica/efectos de los fármacos , Apolipoproteínas/sangre , Modelos Animales de Enfermedad , Humanos , Lipoproteínas/sangre , Persona de Mediana Edad , Conejos , Ratas , Ratas Wistar , Vasoconstrictores/sangre , Vasodilatadores/sangreRESUMEN
The results obtained show the essential changes in functional state of hepatocyte's plasmatic membrane due to the implantation of human ApoA1 gene to the rat liver. The changes in phospholipid composition, hyperpolarization, increase in activity of membrane bound enzymes, cytochrome P-450 and biosynthesis of liver total proteins have been found. The essential changes characterizing cell effect were more marked in the adult rats, and membrane effect in the old ones.
Asunto(s)
Envejecimiento/patología , Hígado/patología , Transfección , Animales , Membrana Celular/enzimología , Membrana Celular/metabolismo , Humanos , Hígado/enzimología , Hígado/metabolismo , Lípidos de la Membrana/metabolismo , Potenciales de la Membrana , Ratas , Ratas WistarRESUMEN
Transfer of human apoAI gene, within the molecular construction which provides its expression, to the liver of adult and aged rats resulted in the appearance of human protein in their blood, and was accompanied by changes in the content of high-density lipoproteins, as well as by the shifts in their protein and lipid composition. Administration of the human ApoAI gene was followed by changes of the vasoactive effects of HDL. Gene implantation is capable of enhancing the direct vasodilatory effects of HDL in old animals, being weakened by ageing, even against the background of normal age changes in the vascular wall tone.
Asunto(s)
Envejecimiento/metabolismo , Apolipoproteína A-I/fisiología , Apoproteínas/metabolismo , Lipoproteínas HDL/metabolismo , Vasoconstrictores/metabolismo , Animales , Apolipoproteína A-I/genética , Técnicas de Transferencia de Gen , Humanos , Masculino , Ratas , Ratas WistarAsunto(s)
Envejecimiento/fisiología , Apolipoproteína A-I/genética , Técnicas de Transferencia de Gen , Lipoproteínas HDL/fisiología , Vasodilatación/fisiología , Envejecimiento/sangre , Envejecimiento/genética , Animales , Aorta Torácica/fisiología , Apolipoproteína A-I/sangre , Apolipoproteína A-I/química , Humanos , Técnicas In Vitro , Lipoproteínas HDL/sangre , Lipoproteínas HDL/química , Lipoproteínas HDL/genética , Músculo Liso Vascular/fisiología , Ratas , Ratas Wistar , Vasodilatación/genéticaRESUMEN
Experiments on adult and old rats have shown that blood lipoproteins (LP) exert a dilatatory effect on isolated-segments of the thoracic aorta in animals of different age. In old versus adult animals, the sensitivity of vessels in all LP fractions (LDL, VLDL and HDL (low, very low and high density LP)) was lower as a result of age changes in the reactivity of vessels. The capacity of HDL to produce a vasodilatory effect decrease with age, which may be linked to changes in the lipid and apolipoprotein composition. The results revealed a decrease in the level of phospholipids and an increase in the amount of total cholesterol in HDL observed in old age. The capacities of LDL and VLDL to exert a vascular dilatatory action remained unchanged with age.
Asunto(s)
Envejecimiento/fisiología , Aorta/efectos de los fármacos , Vasos Sanguíneos/efectos de los fármacos , Lipoproteínas/sangre , Lipoproteínas/farmacología , Envejecimiento/metabolismo , Animales , Relación Dosis-Respuesta a Droga , Masculino , Norepinefrina/farmacología , Ratas , Ratas WistarRESUMEN
Development and regression of experimental atherosclerosis in rabbits is an expressed age-related phenomenon, showing the increase in occurrence and pronouncement of atherosclerotic process with age. A new approach to the disease treatment by means of olivomycin is described. It has shown that while influencing considerably the protein biosynthesis of experimental animal, one can accelerate the regression of atherosclerosis by means of olivomycin and reduce protein and lipid metabolism indicators characterizing the disease development.
Asunto(s)
Envejecimiento/efectos de los fármacos , Arteriosclerosis/tratamiento farmacológico , Olivomicinas/uso terapéutico , Inhibidores de la Síntesis de la Proteína/uso terapéutico , Envejecimiento/sangre , Envejecimiento/patología , Animales , Apolipoproteínas/sangre , Apolipoproteínas/efectos de los fármacos , Arteriosclerosis/sangre , Arteriosclerosis/patología , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Lípidos/sangre , Conejos , Remisión EspontáneaRESUMEN
A comparative biochemical study of the structural-functional peculiarities of genetic apparatus and the content of lipid peroxidation products in the liver nuclei and mitochondria of adult (4.5-5.5 months) and old (22-24 months) CBA mice was carried out. The age-related changes were found as follows: relative content of transcriptionally active and matrix-bound chromatin fractions was decreased, and that of transcriptionally low active fraction was increased; the value of protein/DNA was increased only in transcriptionally active fraction; the value of mitochondrial genome expression coefficient was diminished due to a decreased content of proteins encoded by mtDNA; the concentrations of Schiff bases were elevated both in the nuclei and mitochondria. Possible mechanisms of lipid peroxidation involvement in the above mentioned changes of the nuclear and mitochondrial genetic apparatus are discussed.
Asunto(s)
Envejecimiento/genética , Núcleo Celular/genética , Peroxidación de Lípido/fisiología , Mitocondrias Hepáticas/genética , Animales , Cromatina/genética , ADN Mitocondrial/genética , Masculino , Ratones , Ratones Endogámicos CBA , Relación Estructura-ActividadRESUMEN
Evidences are given that implantation of human apo A-I gene to experimental animals induces essential changes in the functional state of hepatocyte plasmatic phospholipid composition, hyperpolarization development, as well as changes in the Na, K-ATPase and adenylate cyclase activities. The presence of generalized cell reaction is evidenced from the fact than biosynthesis of summary proteins gets enhanced during the above changes.
Asunto(s)
Apolipoproteína A-I/genética , Regulación de la Expresión Génica/fisiología , Técnicas de Transferencia de Gen , Hígado/metabolismo , Adenilil Ciclasas/metabolismo , Animales , Membrana Celular/genética , Membrana Celular/metabolismo , Humanos , Liposomas , Lípidos de la Membrana/metabolismo , Proteínas de la Membrana/metabolismo , Ratas , Ratas Wistar , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Factores de TiempoRESUMEN
Transfer of human ApoA1 gene within the molecular construction which provides its expression, to the liver of the adult and aged rats resulted in the appearance of human protein in their blood, and was accompanied by changes in the content of high-density lipoproteins and of their subclasses HDL(3) and HDL(2), as well as by the shifts in their protein and lipid composition. Synthesis of human ApoA1 was more marked in the organism of adult rats, and gene-regulatory shifts in aged rats.
Asunto(s)
Envejecimiento/genética , Apolipoproteínas A/genética , Lipoproteínas HDL/genética , Transfección/genética , Envejecimiento/sangre , Animales , Apolipoproteína A-I , Apolipoproteínas A/sangre , Clonación Molecular , ADN/genética , Regulación de la Expresión Génica/genética , Regulación de la Expresión Génica/fisiología , Humanos , Lipoproteínas HDL/sangre , Hígado , Plásmidos/genética , RatasRESUMEN
The content of cholesterol, total and individual phospholipids, fatty acid composition, level of lipid peroxidation, as well as viscosity of lipid phase of synaptic membranes isolated from the cerebral cortex were estimated in experiments on adult and old male rats. The content of cholesterol and cholesterol phospholipids ratio were found to increase with age. The total content of phospholipids remained unchanged during ageing, while their composition varied. An increase in the content of minor forms of phospholipids, i.e. phosphatidylserine and phosphatidylinositol, in the sphingomyelin/phosphatidyl ethanolamine ratio and, especially, in the content of lysophosphatidylcholine was found in old vs adult rats. No age-related changes were found in the viscosity of the lipid phase of synaptic membranes with purene used as a fluorescent probe.
Asunto(s)
Envejecimiento/metabolismo , Corteza Cerebral/química , Lípidos/análisis , Membranas Sinápticas/metabolismo , Animales , Colesterol/análisis , Ácidos Grasos/análisis , Peroxidación de Lípido , Masculino , Fosfolípidos/análisis , RatasRESUMEN
To study the age-related relationship between the membrane status and activity of membrane-linked enzymes, the physicochemical properties of plasma membranes and activity of transfer ATPase and adenylate cyclase were assessed in tissues of rats of different ages. The lipid matrix of membranes was found to undergo appropriate changes with age. The most significant shifts are manifested under functional and metabolic stresses. It has been demonstrated that the shifts in the regulated activity of the studied enzymes are induced by changes in membrane interactions. The findings suggest predominantly the membrane mechanisms that determine the insufficiency of adaptation mechanisms in old age.
Asunto(s)
Membrana Celular/análisis , Lípidos/análisis , Adaptación Fisiológica , Adenosina Trifosfatasas/análisis , Adenilil Ciclasas/análisis , Factores de Edad , Animales , Química Encefálica , Colesterol/análisis , Hepatectomía , Hígado/análisis , Miocardio/análisis , Fosfolípidos/análisis , RatasRESUMEN
The study of albino rats aged 6-7 months and 25-27 months revealed the age-related increase of maximal activity (V) of Na+, K+-ATPase of synaptosomal plasma membranes, separated from the cerebral cortex, while the level of Km remained stable. It is shown that in old rats as compared to the adult ones the affinity of Na+, K+-ATPase to sodium ions increases and the character of the ATP hydrolysis schedule changes in the presence of different ration of ions-activators. There are no significant changes in the inhibiting effect of strophantidin K on Na+, K+-ATPase activity of synaptosomal plasma membranes.
Asunto(s)
Envejecimiento/metabolismo , Encéfalo/enzimología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Membranas Sinápticas/enzimología , Adenosina Trifosfato/metabolismo , Animales , Hidrólisis , Cinética , Ratas , ATPasa Intercambiadora de Sodio-Potasio/antagonistas & inhibidoresAsunto(s)
Acetilcolina/farmacología , Envejecimiento/efectos de los fármacos , Encéfalo/efectos de los fármacos , Terminaciones Nerviosas/efectos de los fármacos , Norepinefrina/farmacología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Vasopresinas/farmacología , Animales , Encéfalo/enzimología , Membrana Celular/efectos de los fármacos , Membrana Celular/enzimología , Terminaciones Nerviosas/enzimología , Ratas , Membranas Sinápticas/efectos de los fármacos , Membranas Sinápticas/enzimologíaRESUMEN
Vasopressin regulated in vitro the activity of Na+, K+-ATPase in synaptic membranes from rat brain cortex and brain stem. Low concentrations of the peptide activated the enzyme, high concentrations--inhibited. The effect was most distinct in brain stem. Age-dependent effects of vasopressin on the Na+, K+-ATPase activity were observed. Basal activity of the enzyme was not altered in synaptic membranes with ageing.
Asunto(s)
Encéfalo/enzimología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Membranas Sinápticas/enzimología , Vasopresinas/farmacología , Envejecimiento/fisiología , Animales , Activación Enzimática , Masculino , Ratas , ATPasa Intercambiadora de Sodio-Potasio/antagonistas & inhibidoresRESUMEN
The Na+, K+-ATPase activity in the homogenate and in subcellular fractions of different parts of the brain of adult and old rats was studied in comparison. The content of cholesterol in the above fractions was also determined. In old age the Na+, K+-ATPase activity in the homogenate and microsomal fraction of the cerebral hemispheres' cortex decreases, while the Mg2+-ATPase activity in the cortex microsomal fraction increases. The age-related Na+, K+- and Mg2+-ATPase activity in the myelin of the stem in the synaptic plasma membranes of hemispheres and the brain stem remains unchanged whereas in the myelin fraction of hemispheres it grows. The content of cholesterol in the brain of old rats as compared with adult ones increases in the microsomal fraction and remains unchanged in synaptic membranes. The possible role of age-related modification of lipid component of plasma membranes in the above changes of Na+, K+-ATPase activity is discussed.
Asunto(s)
Envejecimiento , Encéfalo/enzimología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Animales , Tronco Encefálico/enzimología , Hipotálamo/enzimología , Masculino , Ratas , Fracciones Subcelulares/enzimologíaRESUMEN
Content of adenosine phosphate, creatine phosphate, Pi, lactate and ATPase activity were studied in brain of 8-10- and 25-27-months old rats. Content of ATP and ADP and the Na+, K+-ATPase activity were decreased while the level of Pi was increased in rat brain cortex during ageing. Administration of vasopressin caused an increase in lactate, Pi and Na+, K+-ATPase activity, whereas creatine phosphate decreased in the adult rat hypothalamus. Changes in energy metabolism were more pronounced in old rats: simultaneously with the decrease in creatine phosphate and more marked, as compared with adults, increase in Pi and lactate, the content of ATP decreased, ADP and AMP - increased and the Na+, K+-ATPase was distinctly activated in stem and brain cortex.
Asunto(s)
Encéfalo/metabolismo , Metabolismo Energético/efectos de los fármacos , Vasopresinas/farmacología , Nucleótidos de Adenina/metabolismo , Adenosina Trifosfatasas/metabolismo , Envejecimiento , Animales , Encéfalo/enzimología , Lactatos/metabolismo , Masculino , Fosfatos/metabolismo , Fosfocreatina/metabolismo , RatasRESUMEN
Adenosine phosphate and creatine phosphate amount was determined in the brain tissue of 3-4-week, 6-8 month and 26-26 month old mongrel female rats. The maximum ATP and creatine phosphate amount and the minimum of ADP and AMP were found in young rats. In adult rats as compared with the young the ATP amount is the same, the ADP and AMP level rises, that of creative phosphate falls and energy charge decreases. In the brain of old rats the ATP and ADP amount falls, that of creatine phosphate and AMP remains at the level of mature-age animals. Despite a decrease in the ATP amount in the brain at the old age, the Mg, DNP- ATPase activity of mitochondria isolated from brain cortex and stem of the old rats remains at the level typical of adult animals.
Asunto(s)
Nucleótidos de Adenina/metabolismo , Adenosina Trifosfatasas/metabolismo , Encéfalo/crecimiento & desarrollo , Mitocondrias/metabolismo , Fosfocreatina/metabolismo , Adenosina Difosfato/metabolismo , Adenosina Monofosfato/metabolismo , Adenosina Trifosfato/metabolismo , Envejecimiento , Animales , Encéfalo/metabolismo , Femenino , Cinética , RatasRESUMEN
Na, K- and Mg-ATPase activity of the cerebral cortex microsomal fraction has been studied and compared in adult and old rats. The activity of Na, K-ATPase decreases while that of Mg-ATPase increases with age. The total ATPase activity remains unchanged. The effect of acetylcholine on ATPase activity has been found to be age-dependent.