Angiotensin II Requires Zinc and Downregulation of the Zinc Transporters ZnT3 and ZnT10 to Induce Senescence of Vascular Smooth Muscle Cells

Senescence, a hallmark of mammalian aging, is associated with the onset and progression of cardiovascular disease. Angiotensin II (Ang II) signaling and zinc homeostasis dysfunction are increased with age and are linked to cardiovascular disease, but the relationship among these processes has not been investigated. We used a model of cellular senescence induced by Ang II in vascular smooth muscle cells (VSMCs) to explore the role of zinc in vascular dysfunction. We found that Ang II-induced senescence is a zinc-dependent pathway mediated by the downregulation of the zinc transporters ZnT3 and ZnT10, which work to reduce cytosolic zinc. Zinc mimics Ang II by increasing reactive oxygen species (ROS), activating NADPH oxidase activity and Akt, and by downregulating ZnT3 and ZnT10 and inducing senescence. Zinc increases Ang II-induced senescence, while the zinc chelator TPEN, as well as overexpression of ZnT3 or ZnT10, decreases ROS and prevents senescence. Using HEK293 cells, we found that ZnT10 localizes in recycling endosomes and transports zinc into vesicles to prevent zinc toxicity. Zinc and ZnT3/ZnT10 downregulation induces senescence by decreasing the expression of catalase. Consistently, ZnT3 and ZnT10 downregulation by siRNA increases ROS while downregulation of catalase by siRNA induces senescence. Zinc, siZnT3 and siZnT10 downregulate catalase by a post-transcriptional mechanism mediated by decreased phosphorylation of ERK1/2. These data demonstrate that zinc homeostasis dysfunction by decreased expression of ZnT3 or ZnT10 promotes senescence and that Ang II-induced senescence is a zinc and ROS-dependent process. Our studies suggest that zinc might also affect other ROS-dependent processes induced by Ang II, such as hypertrophy and migration of smooth muscle cells

JOURNAL OF SPORTS MEDICINE AND PHYSICAL FITNESS

Background. The purpose of the present study was to compare the aerobic contribution of the Wingate anaerobic test by increasing the test load and power output. Methods. Setting: The study was performed in the Physiology Department of the Faculty of Medicine, Selcuk University. Participants: Thirty sedentary male university students volunteered to this study. Experiments: The subjects performed two Wingate tests against resistance of 75 g.kg(-1) and 95 g.kg(-1) body weight on Monark 818E bicycle ergometer. Breath-by-breath oxygen consumption rates were measured using an automated metabolic measurement chart (Sensormedics 2900). Aerobic contribution was determined by dividing energy equivalence of net oxygen consumption to the total work. Results. The mean total work values obtained from tests performed at 75 g.kg(-1) and 95 g.kg(-1) loads were 13.9+/-1.5 kjoules and 14.5+/-1.8 kjoules (t=2.32, p=0.03). Mean total oxygen consumptions were 765+/-105 ml and 770+/-110 mi, respectively (t=0.24, p=0.81). Assuming 20 % mechanical efficiency for both tests, aerobic contributions were calculated as 19.5+/-3.7 % and 18.9+/-3.7 %, respectively (t=1.01, p=0.30). Conclusions. Although the power outputs of the two tests were different, the difference between aerobic contributions was not statistically significant. So, it was failed to say that the increase in the power outputs might be related to higher contribution of anaerobic processes. However, if different mechanical efficiencies could be used, relationship between aerobic contributions of two tests might have been different

Effects of swimming on erythrocyte rheological properties

Exercise and lactate usually change blood rheology but, effect of swimming on blood rheology is not clear. Blood lactate concentration increases after 400-meter freestyle swimming. In the hemorheological studies, determination of the erythrocyte deformability and aggregation facilitates the evaluation of rheological behaviours of the erythrocytes. The present study was performed to investigate the effects of acute swimming exercise on erythrocyte deformability and aggregation. Seventeen male university swimmers participated in the study. For 400-meter freestyle swimming, participants were asked to swim as fast as they could. Blood lactate concentration, erythrocyte lipid peroxidation and plasma protein oxidation levels, erythrocyte deformability and aggregation, and several haematological parameters were investigated after swimming and they were compared with pre-exercise values. Erythrocyte lipid peroxidation and plasma protein oxidation were unchanged with swimming. Blood lactate concentration increased after 400-meter swimming (p<0.001). Erythrocyte aggregation increased after acute swimming (p<0.01) while erythrocyte deformability was not change. There were no correlations between blood lactate and erythrocyte hemorheological properties before and after swimming.In conclusion, we found that erythrocyte aggregation increased after acute swimming. Further studies are needed to reveal the late effects of acute swimming and to elucidate the effect of swimming different distances on erythrocyte rheological properties

Effects of extremely low-frequency electromagnetic fields (ELF-EMF) exposure on B6C3F1 mice

OBJECTIVE: Long-term exposure study was conducted to investigate the effects of extremely low-frequency electromagnetic field on the tumor promotion process and fertility. METHODS: Ten pregnant C57BL/6NCrj mice were exposed to 50 Hz field 500 mG for 1 week (12 h per day), and 24 male and 42 female B6C3F1mice born from them were further exposed up to 15.5 months. As a control group, 10 pregnant mice were bred without exposure, and 30 produced male and 32 female mice were observed without exposure for the same period. RESULTS: Mean body weights of exposed groups of male and female mice were decreased significantly than those of the control groups. In exposed mice, there was no increased incidence of liver and lung tumor. In female mice, the incidence of chronic myeloid leukemia [3/42 (7 %)] in the exposed group was significantly greater than in the control group. The size of seminiferous tubules in the EMF exposed groups were significantly less than the control group. CONCLUSIONS: These data support the hypothesis that long-term exposure of 50 Hz magnetic fields is a significant risk factor for neoplastic development and fertility in mice