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Review
. 2019 Aug 1;317(2):F444-F455.
doi: 10.1152/ajprenal.00604.2018. Epub 2019 Jun 19.

Effects of reactive oxygen species on renal tubular transport

Affiliations
Review

Effects of reactive oxygen species on renal tubular transport

Agustin Gonzalez-Vicente et al. Am J Physiol Renal Physiol. .

Abstract

Reactive oxygen species (ROS) play a critical role in regulating nephron transport both via transcellular and paracellular pathways under physiological and pathological circumstances. Here, we review the progress made in the past ~10 yr in understanding how ROS regulate solute and water transport in individual nephron segments. Our knowledge in this field is still rudimentary, with basic information lacking. This is most obvious when looking at the reported disparate effects of superoxide ([Formula: see text]) and H2O2 on proximal nephron transport, where there are no easy explanations as to how to reconcile the data. Similarly, we know almost nothing about the regulation of transport in thin descending and ascending limbs, information that is likely critical to understanding the urine concentrating mechanism. In the thick ascending limb, there is general agreement that ROS enhance transcellular reabsorption of NaCl, but we know very little about their effects on the paracellular pathway and therefore Ca2+ and Mg2+ transport. In the distal convoluted tubule, precious little is known. In the collecting duct, there is general agreement that ROS stimulate the epithelial Na+ channel.

Keywords: hydrogen peroxide; reabsorption; sodium; superoxide; water.

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Conflict of interest statement

No conflicts of interest, financial or otherwise, are declared by the authors.

Figures

Fig. 1.
Fig. 1.
Potential explanations for the reports of disparate effects of reactive oxygen species (ROS) on proximal nephron Na+ reabsorption. The effect of ROS may be time dependent, initially stimulating and then inhibiting. Similarly, the effect of ROS may be biphasic with low concentrations stimulating and high concentrations inhibiting. Both ANG II and endothelin have biphasic effects on Na+ reabsorption in this segment.
Fig. 2.
Fig. 2.
Effects of reactive oxygen species (ROS) on Na+-K+-2Cl cotransporter (NKCC2) in the thick ascending limb. Both increases in luminal flow and ANG II stimulate ROS production in this segment. Mitochondria may also be an additional source. ROS increase NKCC2 activity and NaCl reabsorption by stimulating the insertion of additional transporters into the luminal membrane. AT1R, ANG II type 1 receptor.
Fig. 3.
Fig. 3.
Effects of reactive oxygen species (ROS) on epithelial Na+ channel (ENaC) and renal outer medullary K+ channel (ROMK) in the collecting duct. ANG II and aldosterone stimulate ROS production. This enhances ENaC activity via phosphatidylinositol trisphosphate (PIP3). ROS also alleviate the tonic inhibition caused by arachidonic acid. ROS inhibit ROMK activity by activating p38, Erk, and tyrosine kinase (TK). These kinases phosphorylate the channel and reduce its activity. Green arrows represent stimulation. Red arrows indicate inhibition. AT1R, ANG II type 1 receptor; aldo mem receptor, aldosterone membrane receptor.

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