Antioxidants & redox signaling
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Antioxid. Redox Signal. · Mar 2011
ReviewReperfusion injury salvage kinase and survivor activating factor enhancement prosurvival signaling pathways in ischemic postconditioning: two sides of the same coin.
The discovery of ischemic postconditioning (IPost) has rejuvenated the field of cardioprotection. As an interventional strategy to be applied at the onset of myocardial reperfusion, the transition of IPost from a bench-side curiosity to potential clinical therapy has been impressively rapid. ⋯ In this article, the reperfusion injury salvage kinase pathway and the more recently described survivor activating factor enhancement pathway, two apparently distinct signaling pathways that actually interact to convey the IPost stimulus from the cell surface to the mitochondria, where many of the prosurvival and death signals appear to converge. The elucidation of the reperfusion signaling pathways underlying IPost may result in the identification of novel pharmacological targets for cardioprotection.
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Antioxid. Redox Signal. · Mar 2011
Inhibition of LXRα-dependent steatosis and oxidative injury by liquiritigenin, a licorice flavonoid, as mediated with Nrf2 activation.
Liver X receptor-α (LXRα) functions as a major regulator of lipid homeostasis through activation of sterol regulatory element binding protein-1c (SREBP-1c), which promotes hepatic steatosis and steatohepatitis. NF-E2-related factor 2 (Nrf2) is the crucial transcription factor that is necessary for the induction of antioxidant enzymes. This study investigated the potential of liquiritigenin (LQ), a hepatoprotective flavonoid in licorice, to inhibit LXRα-induced hepatic steatosis, and the underlying mechanism of the action. ⋯ LQ was found to activate Nrf2, and the ability of LQ to inhibit LXRα-mediated SREBP-1c activation was reversed by Nrf2 deficiency, which supports the inhibitory role of Nrf2 in LXRα-dependent lipogenesis. Consistently, treatment with other Nrf2 activators or forced expression of Nrf2 also inhibited LXRα-mediated SREBP-1c activation. Our results demonstrate that LQ has an efficacy to activate Nrf2, which contributes to inhibiting the activity of LXRα that leads to SREBP-1c induction and hepatic steatosis.
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Antioxid. Redox Signal. · Nov 2010
Protective role of heme oxygenase-1 against liver damage caused by hepatic ischemia and reperfusion in rats.
This study investigated the time course of heme oxygenase (HO)-1 expression and the role of endogenous HO-1 in hepatic ischemia and reperfusion (I/R). Rats were pretreated with hemin, an HO-1 inducer, and zinc protoporphyrin (ZnPP), an HO-1 inhibitor. Hepatic HO activity increased at 1 h after reperfusion, reaching a maximum at 6 h after reperfusion and then declined. ⋯ These changes were attenuated by hemin but augmented by ZnPP. The levels of serum TNF-α, iNOS, and COX-2 protein and mRNA expressions were upregulated after reperfusion, further enhanced by ZnPP, and suppressed by hemin. HO-1 overexpression protects the liver against I/R injury by modulating oxidative stress and proinflammatory mediators.
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Antioxid. Redox Signal. · Aug 2010
ReviewWomen live longer than men: understanding molecular mechanisms offers opportunities to intervene by using estrogenic compounds.
Women live longer than men. Moreover, females live longer than males in some, but not all, experimental animals. The differences in longevity between genders are related to free radical production. ⋯ These considerations have led us to postulate an extended concept of antioxidant in biology: an antioxidant is any nutritional, physiological, or pharmacological manipulation that increases the expression and activity of antioxidant genes or proteins. Phytoestrogens or other selective estrogen receptor modulators lower age-related diseases and prolong life span, at least in experimental animals. This provides rational bases to study their action in humans further.
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Antioxid. Redox Signal. · Mar 2010
Redox balance and carbonylated proteins in limb and heart muscles of cachectic rats.
In fast- and slow-twitch limb and heart muscles of cachectic rats, redox balance and muscle structure were explored. The nature of the oxidatively modified proteins also was identified in these muscles. Reactive carbonyls, hydroxynonenal (HNE)- and malondialdehyde (MDA)-protein adducts, and antioxidant enzyme levels were determined in limb and heart muscles of cachectic (7 days after inoculation of Yoshida AH-130 ascites hepatoma) and control rats. ⋯ In cachectic rats, compared with the controls: (a) HNE- and MDA-protein adducts levels were greater in gastrocnemius, tibialis anterior, soleus, and heart; (b) in the gastrocnemius, type II fiber size was reduced, and the intensity of carbonylated protein immunostaining was significantly greater in these fibers; and (c) proteins involved in glycolysis, ATP production and distribution, carbon dioxide hydration, muscle contraction, and mitochondrial metabolism were significantly more carbonylated in limb and heart muscles. Cancer cachexia alters redox balance in fast- and slow-twitch limb and heart muscles of rats, inducing increased oxidative modifications of key proteins involved in muscle structure and function. Additionally, it induces a reduction in type II fiber size in the gastrocnemius, which is associated with increased protein oxidation.