Effect of epoetin on HO-1 mRNA level and plasma antioxidants in hemodialysis patients

Calò, L; Stanic, L; Davis, PA; Pagnin, Elisa; Munaretto, G; Fusaro, Maria; Landini, S; Semplicini, Andrea; Piccoli, Antônio

doi:10.5414/cpp41187

Cited by 33 publications

(32 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In hemodialysis patients, the enhancement in antioxidant defenses and increased expression of HO-1 seen upon EPO treatment may reflect a high degree of correlation between hemoglobin and HO-1 expression. This suggests a direct nonerythropoiesis-related effect of EPO (25). These reports are consistent with a linkage between EPO, HO-1, and oxidative stress.…”

Section: Effect Of Ho-1 Interactions With Drug and Growth Factors On supporting

confidence: 85%

Heme oxygenase: the key to renal function regulation

Abraham

Cao

Sacerdoti

et al. 2009

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

Heme oxygenase (HO) plays a critical role in attenuating the production of reactive oxygen species through its ability to degrade heme in an enzymatic process that leads to the production of equimolar amounts of carbon monoxide and biliverdin/bilirubin and the release of free iron. The present review examines the beneficial role of HO-1 (inducible form of HO) that is achieved by increased expression of this enzyme in renal tissue. The influence of the HO system on renal physiology, obesity, vascular dysfunction, and blood pressure regulation is reviewed, and the clinical potential of increased levels of HO-1 protein, HO activity, and HO-derived end products of heme degradation is discussed relative to renal disease. The use of pharmacological and genetic approaches to investigate the role of the HO system in the kidney is key to the development of therapeutic approaches to prevent the adverse effects that accrue due to an impairment in renal function.

show abstract

Section: Effect Of Ho-1 Interactions With Drug and Growth Factors On supporting

confidence: 85%

Heme oxygenase: the key to renal function regulation

Abraham

Cao

Sacerdoti

et al. 2009

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

show abstract

“…In this patient population, the antioxidative capacity of red cells increased (23), as supported by enhanced antioxidant defense enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (43,79,116). SOD converts superoxide anions to H 2 O 2 , and H 2 O 2 is subsequently detoxified by catalase or glutathione peroxidase.…”

Section: How Does Epo Influence the Cardiorenal Connectors?mentioning

confidence: 99%

Erythropoietin and the cardiorenal syndrome: cellular mechanisms on the cardiorenal connectors

Jie

Verhaar²,

Cramer³

et al. 2006

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

We have recently proposed severe cardiorenal syndrome (SCRS), in which cardiac and renal failure mutually amplify progressive failure of both organs. This frequent pathophysiological condition has an extremely poor prognosis. Interactions between inflammation, the renin-angiotensin system, the balance between the nitric oxide and reactive oxygen species and the sympathetic nervous system form the cardiorenal connectors and are cornerstones in the pathophysiology of SCRS. An absolute deficit of erythropoietin (Epo) and decreased sensitivity to Epo in this syndrome both contribute to the development of anemia, which is more pronounced than renal anemia in the absence of heart failure. Besides expression on erythroid progenitor cells, Epo receptors are present in the heart, kidney, and vascular system, in which activation results in antiapoptosis, proliferation, and possibly antioxidation and anti-inflammation. Interestingly, Epo can improve cardiac and renal function. We have therefore reviewed the literature with respect to Epo and the cardiorenal connectors. Indeed, there are indications that Epo can diminish inflammation, reduce renin-angiotensin system activity, and shift the nitric oxide and reactive oxygen species balance toward nitric oxide. Information about Epo and the sympathetic nervous system is scarce. This analysis underscores the relevance of a further understanding of clinical and cellular mechanisms underlying protective effects of Epo, because this will support better treatment of SCRS. heart failure; renal failure; anemia; nitric oxide; reactive oxygen species COEXISTENCE OF RENAL AND cardiac disease is associated with high morbidity and mortality. This pathophysiological condition, in which combined cardiac and renal dysfunction amplifies a progression in the failure of the individual organ, has recently been denoted as severe cardiorenal syndrome (SCRS) (19,20).In patients with declined renal function measured by glomerular filtration rate (GFR), an independent increased risk for cardiovascular events has been found. The hazard ratio for cardiovascular events was 1.4 with a GFR Ͻ60 ml/min and increased with diminished renal function to 2.8 in patients with a GFR Ͻ30 ml/min (99). A 40% higher adjusted risk for adverse cardiovascular outcomes or death was observed in those with relatively minor degrees of renal dysfunction (120). The prevalence of chronic renal failure (CRF) is reportedly high in patients with congestive heart failure (CHF). Furthermore, the prevalence and severity of CRF correlate with the severity of CHF (44, 72). These data support that combined cardiac and renal failure is a profound problem, and a further understanding of the underlying pathophysiological and molecular mechanisms is needed to improve therapy.Our group proposed an interactive network of cardiorenal connectors, i.e., the renin-angiotensin system (RAS), nitric oxide and reactive oxygen species (NO-ROS) balance, the sympathetic nervous system (SNS), and inflammation, as the cornerstones of the pathophysiology o...

show abstract

“…Recently, EPO has been demonstrated to increase HO-1 expression in the kidney (25). Furthermore, increases in monocyte HO-1 mRNA were seen after EPO treatment in hemodialysis patients (10). However, whether EPO upregulates HO-1 expression in the heart is not known.…”

mentioning

confidence: 99%

Role of heme oxygenase-1 in the cardioprotective effects of erythropoietin during myocardial ischemia and reperfusion

Burger¹,

Xiang²,

Hammoud³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

of heme oxygenase-1 in the cardioprotective effects of erythropoietin during myocardial ischemia and reperfusion. Am J Physiol Heart Circ Physiol 296: H84 -H93, 2009; doi:10.1152/ajpheart.00372.2008.-We have recently demonstrated that erythropoietin (EPO) protects cardiomyocytes from apoptosis during myocardial ischemia-reperfusion (I/R). The objective of the present study was to investigate the role of heme oxygenase (HO)-1 in the antiapoptotic effects of EPO. Primary cultures of neonatal mouse cardiomyocytes were subjected to anoxiareoxygenation (A/R). Pretreatment with EPO significantly reduced apoptosis in A/R-treated cells. This reduction in apoptosis was preceded by an increase in the mRNA and protein expression of HO-1. Selective inhibition of HO-1 using chromium mesoporphyrin (CrMP) significantly diminished the ability of EPO to inhibit apoptosis. Cotreatment of EPO with SB-202190, an inhibitor of p38 activation, blocked the EPO-mediated HO-1 expression and antiapoptotic effects, suggesting a p38-dependent mechanism. The in vivo significance of p38 and HO-1 as mediators of EPO's cardioprotection was investigated in mice subjected to myocardial I/R. Pretreatment with EPO decreased infarct size as well as I/R-induced apoptosis in wild-type mice. However, these effects were significantly diminished in HO-1 Ϫ/Ϫ mice. Furthermore, EPO given during ischemia reduced infarct size in mice subjected to I/R, and this effect was blocked by CrMP treatment in wild-type mice. Moreover, inhibition of p38 diminished the cardioprotective effects of EPO. We conclude that upregulation of HO-1 expression via p38 signaling contributes to EPO-mediated cardioprotection during myocardial I/R. myocyte; apoptosis; myocardial infarction; p38 ERYTHROPOIETIN (EPO) has been shown to protect the heart from ischemia-reperfusion (I/R) injury (8, 11). After myocardial infarction, EPO improves cardiac function and reduces ventricular remodeling (41). Our laboratory has demonstrated an important role of protein kinase B (Akt) and endothelial nitric oxide (NO) synthase (eNOS)-derived NO production in the antiapoptotic effects of EPO during myocardial I/R (7). However, since EPO is known to activate multiple intracellular signaling pathways, it is possible that additional mechanisms are involved in EPO's cardioprotective effects.Heme oxygenase (HO) is the rate-limiting enzyme responsible for the breakdown of heme into free ferrous iron, carbon monoxide (CO), and biliverdin, which is ultimately converted to bilirubin. There are three known isoforms of HO. HO-1 is expressed ubiquitously and is inducible. HO-2 is constitutively active and expressed primarily in the brain and testes, and HO-3 is constitutively active as well, but less efficient than the other two oxygenases (47). HO-1 and its byproducts play an important role in regulating cardiomyocyte survival. To this end, the cardiac-specific overexpression of HO-1 reduces oxidative stress and cell death in the heart after myocardial I/R (49). Additionally, HO-1 is known to have a protective ...

show abstract

Effect of epoetin on HO-1 mRNA level and plasma antioxidants in hemodialysis patients

Cited by 33 publications

References 0 publications

Heme oxygenase: the key to renal function regulation

Heme oxygenase: the key to renal function regulation

Erythropoietin and the cardiorenal syndrome: cellular mechanisms on the cardiorenal connectors

Role of heme oxygenase-1 in the cardioprotective effects of erythropoietin during myocardial ischemia and reperfusion

Contact Info

Product

Resources

About