Aerobic exercise training improves oxidative stress and ubiquitin proteasome system activity in heart of spontaneously hypertensive rats

Abstract

The activity of the ubiquitin proteasome system (UPS) and the level of oxidative stress contribute to the transition from compensated cardiac hypertrophy to heart failure in hypertension. Moreover, aerobic exercise training (AET) is an important therapy for the treatment of hypertension, but its effects on the UPS are not completely known. The aim of this study was to evaluate the effect of AET on UPS's activity and oxidative stress level in heart of spontaneously hypertensive rats (SHR). A total of 53 Wistar and SHR rats were randomly divided into sedentary and trained groups. The AET protocol was 5×/week in treadmill for 13 weeks. Exercise tolerance test, non-invasive blood pressure measurement, echocardiographic analyses, and left ventricle hemodynamics were performed during experimental period. The expression of ubiquitinated proteins, 4-hydroxynonenal (4-HNE), Akt, phospho-Akt(ser473), GSK3β, and phospho-GSK3β(ser9) were analyzed by western blotting. The evaluation of lipid hydroperoxide concentration was performed using the xylenol orange method, and the proteasomal chymotrypsin-like activity was measured by fluorimetric assay. Sedentary hypertensive group presented cardiac hypertrophy, unaltered expression of total Akt, phospho-Akt, total GSK3β and phospho-GSK3β, UPS hyperactivity, increased lipid hydroperoxidation as well as elevated expression of 4-HNE but normal cardiac function. In contrast, AET significantly increased exercise tolerance, decreased resting systolic blood pressure and heart rate in hypertensive animals. In addition, the AET increased phospho-Akt expression, decreased phospho-GSK3β, and did not alter the expression of total Akt, total GSK3β, and ubiquitinated proteins, however, significantly attenuated 4-HNE levels, lipid hydroperoxidation, and UPS's activity toward normotensive group levels. Our results provide evidence for the main effect of AET on attenuating cardiac ubiquitin proteasome hyperactivity and oxidative stress in SHR rats.

Impact of Leucine Supplementation on Exercise Training Induced Anti-Cardiac Remodeling Effect in Heart Failure Mice

“…In fact, we [ 5 ] and others [ 4 ] observed cardiac UPS hypoactivation in animals with ischemia-induced CHF. Importantly, severe CHF is also associated with UPS hypoactivation [ 3 , 4 , 29 ] while UPS overactivation is mostly observed in models of compensated cardiac hypertrophy [ 28 , 30 ]. Therefore, our findings suggest that α 2A /α 2C ARKO mice at seven months of age may still be able to degrade modified proteins at the expense of the overactivation of UPS.…”

Spectrophotometric versus spectrofluorometric assessment in the study of the relationships between lipid peroxidation and metabolic dysregulation

“…This is a sensitive and accurate method, with good stability to light/oxygen and with high reproducibility (Gay & Gebicki, ; Mehta, Darji, & Aparnathi, ; Orefice et al., ; Yu, Wang, Zhou, Zhao, & Qiu, ). The FOX method can be employed for determining H 2 O 2 (Nourooz‐Zadeh, ; Sturza et al., ; Yu et al., ), lipid (Ceylan et al., ; Gay & Gebicki, ; Nourooz‐Zadeh, ; Venturini, Simao, & Dichi, ), and protein (Gay & Gebicki, ) hydroperoxides in a wide range of biological samples, from serum (Takci et al., ) and lipoproteins (Erel, ) to cerebrospinal fluid, urine (Erel, ), and tissue homogenates (de Andrade et al., ).…”

Association between exercise habits and subcortical gray matter volumes in healthy elderly people: A population-based study in Japan

“…These meta-analyses showed that aerobic exercise training is associated with modest improvements in cognitive function such as attention, processing speed, executive function and memory. Based on studies using animal models and human subjects, several hypotheses have been proposed to describe the mechanisms behind the beneficial effects of exercise on cognition; these include a reduction in oxidative stress [6] , an increase in growth factor levels (e.g., brain-derived neurotrophic factor, insulin-like growth factor, and vascular endothelial growth factor) [7] , [8] , [9] , [10] , and reduced levels of amyloid-β (Aβ), a key pathogenic factor in Alzheimer's disease (AD) [11] .…”