Prolonged swimming promotes cellular oxidative stress and p66Shc phosphorylation, but does not induce oxidative stress in mitochondria in the rat heart

Abstract

Exercise-induced changes in p66Shc-dependent signaling pathway are still not fully understood. The p66Shc protein is one of the key players in cell signaling, particularly in response to oxidative stress. Therefore, the aim of this study was to investigate the effect of prolonged swimming on the phosphorylation of p66Shc as well as the induction of mitochondrial and cellular oxidative stress in rat hearts. Male Wistar rats were divided into a sedentary control group and an exercise group. The exercised rats swam for 3 hours and were burdened with an additional 3% of their body weight. After the cessation of exercise, their hearts were removed immediately for experiments. The exercise protocol caused increased levels of the following oxidative stress parameters in cardiac cells: DNA damage, protein carbonyls, and lipid dienes. There was also increased phosphorylation of p66Shc without any alterations in Akt and extracellular signal-regulated kinases. Changes in the ferritin L levels and the L to H subunit ratio were also observed in the exercised hearts compared with the control hearts. Despite increased phosphorylation of p66Shc, no significant increase was observed in either mitochondrial H2O2 release or mitochondrial oxidative stress markers. Regardless of the changes in phosphorylation of p66Shc, the antioxidant enzyme activities (superoxide dismutase and catalase) and anti-apoptotic (Bcl2), and pro-apoptotic (Bax) protein levels were not affected by prolonged swimming. Further studies are required to investigate whether p66Shc phosphorylation is beneficial or detrimental to cardiac cells after exercise cessation.

Acute Exercise Induced Mitochondrial H2O2Production in Mouse Skeletal Muscle: Association with p66Shcand FOXO3a Signaling and Antioxidant Enzymes

“…Previous studies have shown that cells and tissues derived from p 66Shc -null mice accumulate significantly less oxidative stress, and the deletion of p 66Shc gene in mice resulted in the decreased formation of mitochondrial H 2 O 2 [ 16 ]. Our finding is also consistent with a latest study demonstrating that a prolonged swimming exercise promoted cellular oxidative stress and p 66Shc phosphorylation in rat heart [ 42 ] and supporting the hypothesis that acute exercise increases H 2 O 2 levels involving upregulating p 66Shc signaling. p 66Shc is a peculiar protein, acting specifically in the mitochondrion as a redox enzyme that generates H 2 O 2 by sequestering electrons from the respiratory chain [ 16 ].…”

New aspects of p66Shc in ischaemia reperfusion injury and other cardiovascular diseases

“…Mitochondria from aged hearts demonstrated a greater enrichment of p66Shc (Ljubicic et al , ). Similarly, intense exercise activated p66Shc; in male Wistar rats, swimming for 3 h per day increased p66Shc phosphorylation, surprisingly without a significant increase in either mitochondrial ROS release or mitochondrial oxidative stress markers or the antioxidant enzyme activities (SOD and catalase) (Ziolkowski et al , ). Thus, regular exercise and ageing affect cardiac p66Shc expression and/or activity; however, the question whether such an increase in p66Shc expression and/or activity relates to cardiomyocyte mitochondria or to mitochondria obtained from other cell types (such as fibroblasts) cannot be resolved using whole cardiac homogenates and remains to be answered using isolated cell preparations.…”

<p>p66shc siRNA Nanoparticles Ameliorate Chondrocytic Mitochondrial Dysfunction in Osteoarthritis</p>

“…p66shc plays a key role in the oxidative stress related to kidney, cardiovascular, and lung disease. [16][17][18][19] p66shc deletion (p66shc −/-) in mice is associated with resistance to oxidative stress and a reduction in p53-dependent apoptosis. p66shc −/mice do not develop emphysema after chronic exposure to smoke, 41 and p66shc deficiency prolongs lifespan, decreasing cytoplasmic ROS levels by activating NADPH oxidase (Nox).…”

“…13 p66shc has been associated with oxidative stress in kidney, cardiovascular, and lung disease. [16][17][18][19] However, the role played by p66shc during articular cartilage degeneration has not been investigated although chondrocytes exhibit reduced mitochondrial membrane potential. 20 Meanwhile, siRNA-loaded nanoparticles (NPs) for drug delivery in various diseases has been in the spotlight recently.…”