American journal of physiology. Renal physiology
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Am. J. Physiol. Renal Physiol. · Mar 2011
Renal cortical albumin gene induction and urinary albumin excretion in response to acute kidney injury.
This study evaluated the potential utility of albuminuria as a "biomarker" of acute kidney injury (AKI) and tested whether AKI induces renal expression of the normally silent albumin gene. Urine albumin concentrations were measured in mice with five different AKI models (maleate, ischemia-reperfusion, rhabdomyolysis, endotoxemia, ureteral obstruction). Albumin gene induction in renal cortex, and in antimycin A-injured cultured proximal tubular cells, was assessed (mRNA levels; RNA polymerase II binding to the albumin gene). ⋯ A correlate in patients was increased urinary α-fetoprotein excretion. We conclude that AKI can unmask, in the kidney, the normally silent renal albumin and α-fetoprotein genes. In addition, the urinary protein data independently indicate that albuminuria, and perhaps α-fetoprotein, have substantial utility as biomarkers of acute tubular injury.
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Am. J. Physiol. Renal Physiol. · Mar 2011
Cyclophosphamide induces NR2B phosphorylation-dependent facilitation on spinal reflex potentiation.
It is well-established that cyclophosphamide (CYP) can sensitize the pelvic afferent nerve arising from the urinary bladder and therefore induce suprapubic pain. To test the possibility that CYP might mediate the development of visceral hypereflexia/hyperalgesia by facilitating spinal activity-dependent neural plasticity, we compared the pelvic-urethra reflex activity and spinal N-methyl-d-aspartate receptor NR2B subunit (NR2B) phosphorylation in rats treated with vehicle solution and CYP. ⋯ When compared with the untreated group, the treatment with small-interfering RNA of NR2B, which decreased the expression of NR2B expression, abolished CYP-dependent reflex facilitation and spinal NR2B phosphorylation. These results suggested that CYP might facilitate spinal reflex potentiation mediated by N-methyl-d-aspartate receptors and participate in the development of visceral hypereflexia/hyperalgesia through nitric oxide- and Cdk5-dependent NR2B phosphorylation at the lumbosacral dorsal horn.