Exercise Increases Markers of Spermatogenesis in Rats Selectively Bred for Low Running Capacity

The oxidative stress effect of exercise training on testis function is under debate. In the present study we used a unique rat model system developed by artificial selection for low and high intrinsic running capacity (LCR and HCR, respectively) to evaluate the effects of exercise training on apoptosis and spermatogenesis in testis. Twenty-four 13-month-old male rats were assigned to four groups: control LCR (LCR-C), trained LCR (LCR-T), control HCR (HCR-C), and trained HCR (HCR-T). Ten key proteins connecting aerobic exercise capacity and general testes function were assessed, including those that are vital for mitochondrial biogenesis. The VO2 max of LCR-C group was about 30% lower than that of HCR-C rats, and the SIRT1 levels were also significantly lower than HCR-C. Twelve weeks of training significantly increased maximal oxygen consumption in LCR by nearly 40% whereas HCR remained unchanged. LCR-T had significantly higher levels of peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1α), decreased levels of reactive oxygen species and increased acetylated p53 compared to LCR-C, while training produced no significant changes for these measures in HCR rats. BAX and Blc-2 were not different among all four groups. The levels of outer dense fibers -1 (Odf-1), a marker of spermatogenesis, increased in LCR-T rats, but decreased in HCR-TR rats. Moreover, exercise training increased the levels of lactate dehydrogenase C (LDHC) only in LCR rats. These data suggest that rats with low inborn exercise capacity can increase whole body oxygen consumption and running exercise capacity with endurance training and, in turn, increase spermatogenesis function via reduction in ROS and heightened activity of p53 in testes

Inhibition of CD34+ cell migration by matrix metalloproteinase-2 during acute myocardial ischemia, counteracted by ischemic preconditioning [version 3; referees: 2 approved]

Background. Mobilization of bone marrow-origin CD34+ cells was investigated 3 days (3d) after acute myocardial infarction (AMI) with/without ischemic preconditioning (IP) in relation to stromal-derived factor-1 (SDF-1α)/ chemokine receptor type 4 (CXCR4) axis, to search for possible mechanisms behind insufficient cardiac repair in the first days post-AMI. Methods. Closed-chest reperfused AMI was performed by percutaneous balloon occlusion of the mid-left anterior descending (LAD) coronary artery for 90min, followed by reperfusion in pigs. Animals were randomized to receive either IP initiated by 3x5min cycles of re-occlusion/re-flow prior to AMI (n=6) or control AMI (n=12). Blood samples were collected at baseline, 3d post-AMI, and at 1-month follow-up to analyse chemokines and mobilized CD34+ cells. To investigate the effect of acute hypoxia, SDF-1α and matrix metalloproteinase (MMP)-2 in vitro were assessed, and a migration assay of CD34+ cells toward cardiomyocytes was performed. Results. Reperfused AMI induced significant mobilisation of CD34+ cells (baseline: 260±75 vs. 3d: 668±180; P<0.001) and secretion of MMP-2 (baseline: 291.83±53.40 vs. 3d: 369.64±72.89; P=0.011) into plasma, without affecting the SDF-1α concentration. IP led to the inhibition of MMP-2 (IP: 165.67±47.99 vs. AMI: 369.64±72.89; P=0.004) 3d post-AMI, accompanied by increased release of SDF-1α (baseline: 23.80±12.36 vs. 3d: 45.29±11.31; P=0.05) and CXCR4 (baseline: 0.59±0.16 vs. 3d: 2.06±1.42; P=0.034), with a parallel higher level of mobilisation of CD34+ cells (IP: 881±126 vs. AMI: 668±180; P=0.026), compared to non-conditioned AMI. In vitro, CD34+ cell migration toward cardiomyocytes was enhanced by SDF-1α, which was completely abolished by 90min hypoxia and co-incubation with MMP-2. Conclusions. Non-conditioned AMI induces MMP-2 release, hampering the ischemia-induced increase in SDF-1α and CXCR4 by cleaving the SDF-1α/CXCR4 axis, with diminished mobilization of the angiogenic CD34+ cells. IP might influence CD34+ cell mobilization via inhibition of MMP-2

Long Term Osmotic Mini Pump Treatment with Alpha-MSH Improves Myocardial Function in Zucker Diabetic Fatty Rats

The present investigation evaluates the cardiovascular effects of the anorexigenic mediator alpha-melanocyte stimulating hormone (MSH), in a rat model of type 2 diabetes. Osmotic mini pumps delivering MSH or vehicle, for 6 weeks, were surgically implanted in Zucker Diabetic Fatty (ZDF) rats. Serum parameters, blood pressure, and weight gain were monitored along with oral glucose tolerance (OGTT). Echocardiography was conducted and, following sacrifice, the effects of treatment on ischemia/reperfusion cardiac injury were assessed using the isolated working heart method. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was measured to evaluate levels of oxidative stress, and force measurements were performed on isolated cardiomyocytes to determine calcium sensitivity, active tension and myofilament co-operation. Vascular status was also evaluated on isolated arterioles using a contractile force measurement setup. The echocardiographic parameters ejection fraction (EF), fractional shortening (FS), isovolumetric relaxation time (IVRT), mitral annular plane systolic excursion (MAPSE), and Tei-index were significantly better in the MSH-treated group compared to ZDF controls. Isolated working heart aortic and coronary flow was increased in treated rats, and higher Hill coefficient indicated better myofilament co-operation in the MSH-treated group. We conclude that MSH improves global heart functions in ZDF rats, but these effects are not related to the vascular status

Running distance (A), VO2max (B) of LCR rats.

<p>Maximal relative oxygen uptake (VO₂max; ml/kg/min)(<b>A</b>), and running distance (m) (<b>B</b>), for low capacity runner (LCR) and high capacity runner rats were measured every second week across a 12 week exercise training period and during the two weeks of treadmill habituation. Control LCR (LCR-C), trained LCR (LCR-T), high capacity control (HCR-C) and trained (HCR-T) groups. Values are means ± SD for six animals per group <b>*</b>Significantly different from control group, +Significantly different from trained group, #Significantly different fromthe starting value, p<0.05.</p

Oxidative stress markers.

<p>Rat gastrocnemius muscle was stained with dichlorodihydrofluoresceindiacetate (H₂DCFDA) to measure relative steady-state oxidant levels and redox-active iron release levels (both increase DCF fluorescence) as an estimate of levels of reactive oxygen species (ROS).Control LCR (LCR-C), trained LCR (LCR-T), high capacity control (HCR-C) and trained (HCR-T) groups. Values are means ± SD for six animals per group <b>*</b>Significantly different from control group, +Significantly different from trained group, p<0.05.</p

Apoptosis markers.

<p>The ratio of acetylated p53/and total p53 (<b>A</b>) levelsrelated to genetic stability.Bax (<b>B</b>) and Blc-2 (<b>C</b>) were evaluated to assess the levels of apoptosis. Control LCR (LCR-C), trained LCR (LCR-T), high capacity control (HCR-C) and trained (HCR-T) groups. Values are means ± SD for six animals per group <b>*</b>Significantly different from control group, +Significantly different from trained group, p<0.05.</p