Swimming exercise inhibits myocardial ER stress in the hearts of aged mice by enhancing cGMP‑PKG signaling

Abstract

The purpose of the present study was to explore aging-associated cardiac dysfunction and the possible mechanism by which swimming exercise modulates cardiac dysfunction in aged mice. aged mice were divided into two groups: i) aged mice; and ii) aged mice subjected to swimming exercises. another cohort of 4-month-old male mice served as the control group. cardiac structure and function in mice were analyzed using hematoxylin and eosin staining, and echocardiography. The levels of oxidative stress were determined by measuring the levels of superoxide dismutase, malondialdehyde and reactive oxygen species (roS). levels of the endoplasmic reticulum (er) stress-related protein PKr-like er kinase, glucose-regulated protein 78 and c/eBP homologous protein were determined to evaluate the level of er stress. The aged group exhibited an abnormal cardiac structure and decreased cardiac function, both of which were ameliorated by swimming exercise. The hearts of the aged mice exhibited pronounced oxidative and er stress, which were ameliorated by exercise, and was accompanied by the reactivation of myocardial cGMP and suppression of cGMP-specific phosphodiesterase type 5 (Pde5). The inhibition of Pde5 attenuated age-induced cardiac dysfunction, blocked roS production and suppressed ER stress. An ER stress inducer abolished the beneficial effects of the swimming exercise on cardiac function and increased roS production. The present study suggested that exercise restored cardiac function in mice with age-induced cardiac dysfunction by inhibiting oxidative stress and er stress, and increasing cGMP-protein kinase G signaling.

Decreased miR-132 plays a crucial role in diabetic encephalopathy by regulating the GSK-3β/Tau pathway

“…The main operating methods followed previous experiments with minor variations [ 52 , 53 ] using primary antibodies listed in Section 2.2. Briefly, frozen animal heart tissues were homogenized in ice-cold riPa lysis buffer.…”

Phosphorylation Modifications Regulating Cardiac Protein Quality Control Mechanisms

“…The cardioprotective abilities of PKG have been demonstrated in the setting of various cardiac diseases including PO, MI, ischemia/reperfusion injury and is the subject of many clinical trials as a heart failure treatment (Kokkonen-Simon et al, 2018;Dunkerly-Eyring and Kass, 2019;Pinilla-Vera et al, 2019;Oeing et al, 2020b). ER stress during cardiac aging and heart failure was abrogated by activating PKG by way of sildenafil treatment (PDE5 inhibition) in isoproterenol-induced or TACinduced hypertrophy, or swimming exercise (Gong et al, 2013;Chang et al, 2020). A new signaling paradigm was revealed in early 2019 whereby PKG phosphorylates TSC2 (aka tuberin) at serine 1365, which results in mTORC1 inhibition but only in the presence of a pathological stimulus (Ranek et al, 2019).…”

Mitochondrial Membrane Intracellular Communication in Healthy and Diseased Myocardium

“…Participation in secondary prevention lifestyle changes such as exercise training and caloric restriction has been shown to protect against cardiac risk factors and improve the quality of life of individuals (Clark et al, 2005 ). Swimming exercise in aged mice suppressed ER stress responses delaying ROS-mediated cell damage by enhancing antioxidation mechanisms via increased superoxide dismutase (Chang et al, 2020 ). Resistance exercise and aerobic exercise significantly decreased the expression of ER stress markers (CHOP, eIF2α, and PERK) (Kim et al, 2018 ).…”