Nitric oxide production by mouse renal tubules can be increased by a sodium-dependent mechanism

Kempson, Stephen A.; Thompson, Nathan; Pezzuto, Laura; Bohlen, H. G.

doi:10.1016/j.niox.2007.05.002

Cited by 11 publications

(5 citation statements)

References 44 publications

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“…In test chambers, neither nitrite nor nitrate at physiological concentrations influence the NOsensitive microelectrode (5), nor do the electrodes respond to arginine and lysine at physiological and vasoactive supraphysiological concentrations (34,45) and do not detect signals from frozen and rewarmed intestinal tissue (5). In this study, as well as others using nitroarginine analogs and lysine to suppress L-arginine transport (1,34,45), the measured signal interpreted as NO is substantially decreased, but not driven to nearly undectable as is possible with in vitro preparations (13,24). We have suspected for some time that the residual [NO] after localized suppression of eNOS is due to NO from blood.…”

Section: Discussioncontrasting

confidence: 42%

Transfer of nitric oxide by blood from upstream to downstream resistance vessels causes microvascular dilation

Bohlen¹,

Zhou

Unthank

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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The discovery that hemoglobin, albumin, and glutathione carry and release nitric oxide (NO) may have consequences for movement of NO by blood within microvessels. We hypothesize that NO in plasma or bound to proteins likely survives to downstream locations. To confirm this hypothesis, there must be a finite NO concentration ([NO]) in arteriolar blood, and upstream resistance vessels must be able to increase the vessel wall [NO] of downstream arterioles. Arteriolar blood NO was measured with NO-sensitive microelectrodes, and vessel wall [NO] was consistently 25-40% higher than blood [NO]. Localized suppression of NO production in large arterioles over 500-1,000 microm with L-nitroarginine reduced the [NO] approximately 40%, indicating as much as 60% of the wall NO was from blood transfer. Flow in mesenteric arteries was elevated by occlusion of adjacent arteries to induce a flow-mediated increase in arterial NO production. Both arterial wall and downstream arteriolar [NO] increased and the arterioles dilated as the blood [NO] was increased. To study receptor-mediated NO generation, bradykinin was locally applied to upstream large arterioles and NO measured there and in downstream arterioles. At both sites, [NO] increased and both sets of vessels dilated. When isoproterenol was applied to the upstream vessels, they dilated, but neither the [NO] or diameter downstream arterioles increased. These observations indicate that NO can move in blood from upstream to downstream resistance vessels. This mechanism allows larger vessels that generate large [NO] to influence vascular tone in downstream vessels in response to both flow and receptor stimuli.

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Section: Discussioncontrasting

confidence: 42%

Transfer of nitric oxide by blood from upstream to downstream resistance vessels causes microvascular dilation

Bohlen¹,

Zhou

Unthank

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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“…The common mechanism is endocytic removal of pre-existing BGT1 protein from the basolateral plasma membrane which would be useful when cellular accumulation of betaine was no longer required. In contrast, nitric oxide which is produced in the renal medulla is response to hypertonic extracellular NaCl (Kempson et al, 2007 ) upregulates BGT1 transport in MDCK cells. The mechanism is not understood but the result is increased delivery of BGT1 protein to the plasma membrane, as detected by total internal reflection fluorescence (TIRF) microscopy (Kempson et al, 2011 ).…”

Section: Bgt1 and Betaine In Kidneymentioning

confidence: 99%

The betaine/GABA transporter and betaine: roles in brain, kidney, and liver

2014

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The physiological roles of the betaine/GABA transporter (BGT1; slc6a12) are still being debated. BGT1 is a member of the solute carrier family 6 (the neurotransmitter, sodium symporter transporter family) and mediates cellular uptake of betaine and GABA in a sodium- and chloride-dependent process. Most of the studies of BGT1 concern its function and regulation in the kidney medulla where its role is best understood. The conditions here are hostile due to hyperosmolarity and significant concentrations of NH4Cl and urea. To withstand the hyperosmolarity, cells trigger osmotic adaptation, involving concentration of a transcriptional factor TonEBP/NFAT5 in the nucleus, and accumulate betaine and other osmolytes. Data from renal cells in culture, primarily MDCK, revealed that transcriptional regulation of BGT1 by TonEBP/NFAT5 is relatively slow. To allow more acute control of the abundance of BGT1 protein in the plasma membrane, there is also post-translation regulation of BGT1 protein trafficking which is dependent on intracellular calcium and ATP. Further, betaine may be important in liver metabolism as a methyl donor. In fact, in the mouse the liver is the organ with the highest content of BGT1. Hepatocytes express high levels of both BGT1 and the only enzyme that can metabolize betaine, namely betaine:homocysteine –S-methyltransferase (BHMT1). The BHMT1 enzyme removes a methyl group from betaine and transfers it to homocysteine, a potential risk factor for cardiovascular disease. Finally, BGT1 has been proposed to play a role in controlling brain excitability and thereby represents a target for anticonvulsive drug development. The latter hypothesis is controversial due to very low expression levels of BGT1 relative to other GABA transporters in brain, and also the primary location of BGT1 at the surface of the brain in the leptomeninges. These issues are discussed in detail.

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“…tubules by stimulating Na-H exchange and Na,K-ATPase [9]. Monensin-treated renal cells have been used as a model to study the mechanisms underlying Na absorption in the renal proximal tubules [4,15]. Using HEK293 cells as a model free of immune interference, we found that monensin increases the mitochondrial Complex II, ROS and MnSOD activities.…”

Section: Introductionmentioning

confidence: 92%

EAE-induced upregulation of mitochondrial MnSOD is associated with increases of mitochondrial SGK1 and Tom20 protein in the mouse kidney cortex

2019

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Our previous demonstration that severe experimental autoimmune encephalomyelitis (EAE) increases MnSOD protein abundance in the mouse kidney cortex led this study to elucidate the underlying mechanism with monensin-treated HEK293 cells as a model. Severe EAE increases mitochondrial protein abundance of SGK1 kinase and Tom20, a critical subunit of mitochondrial translocase in the renal cortex. In HEK293 cells, catalase inhibits monensin-induced increases of mitochondrial SGK1 and Tom20 protein levels. Further, GSK650394, a specific inhibitor of SGK1 reduces monensin-induced increase of mitochondrial protein abundance of Tom20 and MnSOD. Finally, RNAi of Tom20 reduces the effect of monensin on MnSOD. MnSOD and Tom20 physically associate with each other. In conclusion, in HEK293 cells, mitochondrial reactive oxygen species increase protein abundance of mitochondrial SGK1, which leads to a rise of mitochondrial Tom20, resulting in importing MnSOD protein into the mitochondria. This could be a mechanism by which severe EAE up-regulates mitochondrial MnSOD in the kidney cortex. Keywords Na,K-ATPase • Reactive oxygen species • Experimental autoimmune encephalomyelitis • Ouabain • Monensin • HEK293 cells Abbreviations EAE Experimental autoimmune encephalomyelitis MnSOD Manganese superoxide dismutase ROS Reactive oxygen species Tom20 Translocase of the outer membrane subunit 20

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Nitric oxide production by mouse renal tubules can be increased by a sodium-dependent mechanism

Cited by 11 publications

References 44 publications

Transfer of nitric oxide by blood from upstream to downstream resistance vessels causes microvascular dilation

Transfer of nitric oxide by blood from upstream to downstream resistance vessels causes microvascular dilation

The betaine/GABA transporter and betaine: roles in brain, kidney, and liver

EAE-induced upregulation of mitochondrial MnSOD is associated with increases of mitochondrial SGK1 and Tom20 protein in the mouse kidney cortex

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