Erythropoietin Receptor Signaling Mitigates Renal Dysfunction-Associated Heart Failure by Mechanisms Unrelated to Relief of Anemia

ObjectivesWe examined the effect of asialoerythropoietin (asialoEPO), a nonerythrogenic derivative of erythropoietin (EPO), on renal dysfunction-associated heart failure.BackgroundAlthough EPO is known to exert beneficial effects on cardiac function, the clinical benefits in patients with chronic kidney disease are controversial. It remains to be addressed whether previously reported outcomes were the result of relief of the anemia, adverse effects of EPO, or direct cardiovascular effects.MethodsMice underwent 5/6 nephrectomy to cause renal dysfunction. Eight weeks later, when renal dysfunction was established, anemia and cardiac dysfunction and remodeling were apparent. Mice were then assigned to receive saline (control), recombinant human erythropoietin (rhEPO) at 5,000 IU (714 pmol)/kg, or asialoEPO at 714 pmol/kg, twice/week for 4 weeks.ResultsAlthough only rhEPO relieved the nephrectomy-induced anemia, both rhEPO and asialoEPO significantly and similarly mitigated left ventricular dilation and dysfunction. The hearts of rhEPO- or asialoEPO-treated mice showed less hypertrophy, reflecting decreases in cardiomyocyte hypertrophy and degenerative subcellular changes, as well as significant attenuation of fibrosis, leukocyte infiltration, and oxidative deoxyribonucleic acid damage. These phenotypes were accompanied by restored expression of GATA-4, sarcomeric proteins, and vascular endothelial growth factor and decreased inflammatory cytokines and lipid peroxidation. Finally, myocardial activation was observed of extracellular signal-regulated protein kinase and signal transducer and activator of transcription pathways in the treated mice.ConclusionsEPO receptor signaling exerts direct cardioprotection in an animal model of renal dysfunction-associated heart failure, probably by mitigating degenerative, pro-fibrosis, inflammatory, and oxidative processes but not through relief of anemia

Contribution of Root Hair Development to Sulfate Uptake in <i>Arabidopsis</i>

Root hairs often contribute to nutrient uptake from environments, but the contribution varies among nutrients. In Arabidopsis, two high-affinity sulfate transporters, SULTR1;1 and SULTR1;2, are responsible for sulfate uptake by roots. Their increased expression under sulfur deficiency (&#8722;S) stimulates sulfate uptake. Inspired by the higher and lower expression, respectively, of SULTR1;1 in mutants with more (werwolf [wer]) and fewer (caprice [cpc]) root hairs, we examined the contribution of root hairs to sulfate uptake. Sulfate uptake rates were similar among plant lines under both sulfur sufficiency (+S) and &#8722;S. Under &#8722;S, the expression of SULTR1;1 and SULTR1;2 was negatively correlated with the number of root hairs. These results suggest that both &#8722;S-induced SULTR expression and sulfate uptake rates were independent of the number of root hairs. In addition, we observed (1) a negative correlation between primary root lengths and number of root hairs and (2) a greater number of root hairs under &#8722;S than under +S. These observations suggested that under both +S and &#8722;S, sulfate uptake was influenced by the root biomass rather than the number of root hairs