Oxidative stress and antioxidant defense mechanisms linked to exercise during cardiopulmonary and metabolic disorders

Abstract

Oxidative stress has been implicated in the pathophysiology of multiple human diseases, in addition to the aging process. Although various stimuli exist, acute exercise is known to induce a transient increase in reactive oxygen and nitrogen species (RONS), evident by several reports of increased oxidative damage following acute bouts of aerobic and anaerobic exercise. Although the results are somewhat mixed and appear disease dependent, individuals with chronic disease experience an exacerbation in oxidative stress following acute exercise when compared to healthy individuals. However, this increased oxidant stress may serve as a necessary "signal" for the upregulation in antioxidant defenses, thereby providing protection against subsequent exposure to prooxidant environments within susceptible individuals. Here we present studies related to both acute exercise-induced oxidative stress in those with disease, in addition to studies focused on adaptations resulting from increased RONS exposure associated with chronic exercise training in persons with disease.

Keywords: antioxidant; cardiovascular disease; chronic obstructive pulmonary disease; cigarette smoking; diabetes; exercise; obesity; reactive oxygen species.

Figure 1

Potential changes in antioxidant defense as a result of chronic exercise training. Exercise-induced RONS production results in the activation of IκB kinase (IKK), secondary to the activation of mitogen activated protein kinases (MAPK). IKK then phosphorylates the inhibitory subunit of nuclear transcription factor-κB (NFκB), thus releasing it to migrate to the nucleus. Once inside the nucleus, NFκB promotes the transcription of several antioxidant enzymes [manganese superoxide dismutase (MnSOD), inducible nitric oxide synthase (iNOS), glumatylcysteine synthetase (GCS)]. Messenger RNA (mRNA) is then synthesized for each enzyme, exits the nucleus and undergoes translation, ultimately resulting in an upregulation in antioxidant protein expression and improved antioxidant defense.