AIM: To systematically investigate if cGMP/cGMP- dependent protein kinase G (PKG) signaling pathway may participate in dendroaspis natriuretic peptide (DNP)-induced relaxation of gastric circular smooth muscle. METHOD...AIM: To systematically investigate if cGMP/cGMP- dependent protein kinase G (PKG) signaling pathway may participate in dendroaspis natriuretic peptide (DNP)-induced relaxation of gastric circular smooth muscle. METHODS: The content of cGMP in guinea pig gastric antral smooth muscle tissue and perfusion solution were measured using radioimmunoassay; spontaneous contraction of gastric antral circular muscles recorded using a 4-channel physiograph; and Ca2+-activated K+ currents (IK(Ca)) and spontaneous transient outward currents (STOCs) in isolated gastric antral myocytes were recorded using the whole-cell patch clamp technique. RESULTS: DNP markedly enhanced cGMP levels in gastric antral smooth muscle tissue and in the perfusion medium. DNP induced relaxation in gastricantral circular smooth muscle, which was inhibited by KT5823, a cGMP-dependent PKG inhibitor. DNP increased IK(Ca). This effect was almost completely blocked by KT5823, and partially blocked by LY83583, an inhibitor of guanylate cyclase to change the production of cGMP. DNP also increased STOCs. The effect of DNP on STOCs was abolished in the presence of KT5823, but not affected by KT-5720, a PKA-specific inhibitor. CONCLUSION: DNP activates IK(Ca) and relaxes guinea-pig gastric antral circular smooth muscle via the cGMP/PKG-dependent singling axis instead of cAMP/ PKA pathway.展开更多
Oxidative stress is a health condition that could potentially harm the patient, and it is defined as the lack of balance between the production of oxygen free radicals, which rises, and antioxidant defenses, which are...Oxidative stress is a health condition that could potentially harm the patient, and it is defined as the lack of balance between the production of oxygen free radicals, which rises, and antioxidant defenses, which are in decrease. Metabolic syndrome implies a variety of risk factors that are based on abdominal obesity and insulin resistance. Moreover, the importance of metabolic syndrome is emphasized due to the fact that it presents an increase in oxidative stress, which is produced by the sum of alterations that each risk factor produces within the metabolic syndrome pathology. Reducing oxidative stress in these patients is currently one of the most interesting challenges of cardiovascular and metabolic therapeutics, because it is a molecular biology alteration that is not generally diagnosed and, therefore, not treated. The increasing incidence of overweight and obesity cause an increase in the incidence of metabolic syndrome, thus turning into a huge problem that keeps growing at alarming proportions. This syndrome＇s incidence oscillates between 20 and 40%, depending on the gender, age, ethnic group, and diagnostic criteria used for the definition of the disease. Prospective studies show that metabolic syndrome doubles the risk of cardiovascular disease and causes a five-fold increase in the risk of developing type 2 diabetes. With the aim of decreasing the oxidative stress caused by metabolic syndrome, we investigated the effect of antioxidant protection in DNA repair and cell membranes through the use of blueberry extract, which is the fruit with the highest antioxidant capacity, in patients with metabolic syndrome. Thirty patients were studied for a period of 6 months of intervention, and it could be demonstrated that they showed a highly significant decrease in the damage produced to the DNA, which was measured by the urinary excretion of 8-hydroxy-2＇-deoxyguanosine （8-OHdG） and the damage caused to the vascular endothelium and cell membranes, which was measured through the urinary excretion of F2-isoprostane. Based on our knowledge, this investigation is the first one to show that lyophilized blueberry extract （BlueKing~） as a dietary supplement, with meals, is an additional therapeutic tool of great value for the treatment of oxidative stress through DNA and cell membrane protection in patients with metabolic syndrome.展开更多
基金The National Natural Science Foundation of China, No. 30800382the Youth Science Foundation of Dalian to Professor Hui-Shu Guo, No. 2006B3NS218
文摘AIM: To systematically investigate if cGMP/cGMP- dependent protein kinase G (PKG) signaling pathway may participate in dendroaspis natriuretic peptide (DNP)-induced relaxation of gastric circular smooth muscle. METHODS: The content of cGMP in guinea pig gastric antral smooth muscle tissue and perfusion solution were measured using radioimmunoassay; spontaneous contraction of gastric antral circular muscles recorded using a 4-channel physiograph; and Ca2+-activated K+ currents (IK(Ca)) and spontaneous transient outward currents (STOCs) in isolated gastric antral myocytes were recorded using the whole-cell patch clamp technique. RESULTS: DNP markedly enhanced cGMP levels in gastric antral smooth muscle tissue and in the perfusion medium. DNP induced relaxation in gastricantral circular smooth muscle, which was inhibited by KT5823, a cGMP-dependent PKG inhibitor. DNP increased IK(Ca). This effect was almost completely blocked by KT5823, and partially blocked by LY83583, an inhibitor of guanylate cyclase to change the production of cGMP. DNP also increased STOCs. The effect of DNP on STOCs was abolished in the presence of KT5823, but not affected by KT-5720, a PKA-specific inhibitor. CONCLUSION: DNP activates IK(Ca) and relaxes guinea-pig gastric antral circular smooth muscle via the cGMP/PKG-dependent singling axis instead of cAMP/ PKA pathway.
文摘Oxidative stress is a health condition that could potentially harm the patient, and it is defined as the lack of balance between the production of oxygen free radicals, which rises, and antioxidant defenses, which are in decrease. Metabolic syndrome implies a variety of risk factors that are based on abdominal obesity and insulin resistance. Moreover, the importance of metabolic syndrome is emphasized due to the fact that it presents an increase in oxidative stress, which is produced by the sum of alterations that each risk factor produces within the metabolic syndrome pathology. Reducing oxidative stress in these patients is currently one of the most interesting challenges of cardiovascular and metabolic therapeutics, because it is a molecular biology alteration that is not generally diagnosed and, therefore, not treated. The increasing incidence of overweight and obesity cause an increase in the incidence of metabolic syndrome, thus turning into a huge problem that keeps growing at alarming proportions. This syndrome＇s incidence oscillates between 20 and 40%, depending on the gender, age, ethnic group, and diagnostic criteria used for the definition of the disease. Prospective studies show that metabolic syndrome doubles the risk of cardiovascular disease and causes a five-fold increase in the risk of developing type 2 diabetes. With the aim of decreasing the oxidative stress caused by metabolic syndrome, we investigated the effect of antioxidant protection in DNA repair and cell membranes through the use of blueberry extract, which is the fruit with the highest antioxidant capacity, in patients with metabolic syndrome. Thirty patients were studied for a period of 6 months of intervention, and it could be demonstrated that they showed a highly significant decrease in the damage produced to the DNA, which was measured by the urinary excretion of 8-hydroxy-2＇-deoxyguanosine （8-OHdG） and the damage caused to the vascular endothelium and cell membranes, which was measured through the urinary excretion of F2-isoprostane. Based on our knowledge, this investigation is the first one to show that lyophilized blueberry extract （BlueKing~） as a dietary supplement, with meals, is an additional therapeutic tool of great value for the treatment of oxidative stress through DNA and cell membrane protection in patients with metabolic syndrome.
