Acute exercise activates myocardial nuclear factor kappa B

Abstract

The myocardial stress response to exercise is dependent on exercise intensity and thus understanding the molecular responses between various exercise intensity levels might aid in exercise prescription. Nuclear factor kappa B (NF-κB) is a ubiquitous transcription factor that mediates a variety of cellular processes including inflammation, immune responses, apoptosis and cell growth/development. NF-κB can be comprised of homo- and/or heterodimers formed from five distinct proteins: p50 (NF-κB1), p52 (NF-κB2), RelA (p65), c-Rel, and RelB. NF-κB is located in the cytoplasm and kept inactive by inhibitory proteins but following the exposure to a myriad of stimuli, an activated NF-κB dimer translocates to the nucleus and exerts transcriptional effects on upwards of 150 genes. To examine the activation of NF-κB in the myocardium following exercise, male Sprague-Dawley rats (n = 24) were exercised by treadmill running at 20 m/min for 30 min or 30 m/min for 20 min. At 0, 2, or 24 h following exercise, animals were anesthetized, hearts excised and immediately frozen in liquid nitrogen. Portions of hearts were homogenized, protein concentrations determined and extracts assayed for NF-κB activation (DNA binding activity) using electrophoretic mobility shift assays (EMSA). Visual examination of EMSA autoradiographs revealed an enhanced NF-κB activation in the hearts from exercised animals when compared with non-running controls. Subsequent supershift analyses using antibodies specific for NF-κB subunits showed the higher intensity exercise was associated with p65 (RelA) in the activated NF-κB complex while the NF-κB complex in hearts from animals exercised at the lower intensity was comprised primarily of p50. These data suggest exercise is capable of activating myocardial NF-κB and that a threshold for the activation of specific NF-κB subunits may exist.

Impaired Circulating Angiogenic Cells Mobilization and Metalloproteinase-9 Activity after Dynamic Exercise in Early Metabolic Syndrome

“…In fact, levels of sE-selectin and sICAM-1 were still increased after exercise in subjects with early MetS, which contributes to apoptosis or loss of CACs functionality. Acute exercise induces a transient inflammatory response through the increase in several cytokines such as interleukin-6, tumor necrosis factor- α , C-reactive protein [ 14 ], and nuclear factor kappa B [ 28 ] and oxidative stress [ 29 ] in healthy subjects and in subjects with coronary artery disease [ 30 ]. In contrast, chronic repetitive exercise, that is, physical training, induces the development of an adaptation to the acute stress of exercise bouts [ 31 ] and reduces proinflammatory cytokine basal levels while inducing the expression of antioxidant and anti-inflammatory variables in the vessel [ 30 ].…”

Functional Networks of Nucleocytoplasmic Transport-Related Genes Differentiate Ischemic and Dilated Cardiomyopathies. A New Therapeutic Opportunity

“…It is interesting to point out that NFKB2 gene presents an opposite correlation in ICM and DCM. This could be attributed to the fact that NFKB2 encodes a subunit of the transcription factor complex nuclear factor-kappa-B (NFκB), which could function as both a transcriptional activator and repressor depending on its dimerization partner [48] , [49] , and that the transcription factor complex NFκB when activated by a myriad of stimuli exerts its transcriptional effects on upwards of 150 genes [50] .…”

The Physiological Effect of n-3 Polyunsaturated Fatty Acids (n-3 PUFAs) Intake and Exercise on Hemorheology, Microvascular Function, and Physical Performance in Health and Cardiovascular Diseases; Is There an Interaction of Exercise and Dietary n-3 PUFA Intake?

“…The effect of exercise on NF-κB transcriptional activity is dependent on the type and intensity of physical activity. An acute bout of exercise activates myocardial NF-κB and increases toll-like receptor 4 signaling leading to inflammation (Balan and Locke, 2011; Cristi-Montero et al, 2012; Vella et al, 2012), while moderate exercise reduces NF-κB signaling and activates the SIRT1-AMPK-PGC1α axis, resulting in decreased inflammation and reduced muscle loss (Liu and Chang, 2018). All of this has been summarized in Figure 5.…”