title: 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.
authors: Universidade Federal de São Paulo- Departamento de Biociências, Silva Jardim, 136-Vl. Mathias, Santos, SP, 11015-020, Brazil.
authors: Luiz Henrique Soares
authors: LH
authors: de Andrade
authors: Wilson Max Almeida Monteiro
authors: WM
authors: de Moraes
authors: Eduardo Hiroshi
authors: EH
authors: Matsuo Junior
authors: Elizabeth
authors: E
authors: de Orleans Carvalho de Moura
authors: Hanna Karen Moreira
authors: HK
authors: Antunes
authors: Jairo
authors: J
authors: Montemor
authors: Ednei Luiz
authors: EL
authors: Antonio
authors: Danilo Sales
authors: DS
authors: Bocalini
authors: Andrey Jorge
authors: AJ
authors: Serra
authors: Paulo José Ferreira
authors: PJ
authors: Tucci
authors: Patricia Chakur
authors: PC
authors: Brum
authors: Alessandra
authors: A
authors: Medeiros
mesh_terms: D000818:Animals; D048429:Cell Size; D005081:Exercise Therapy; D006973:Hypertension / Q000378:metabolism / Q000628:therapy*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000473:pathology; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D059748:Proteolysis; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination; D056811:Unfolded Protein Response
chemical_list: D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex
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