New inhibitors of the Kvβ2 subunit from mammalian Kv1 potassium channels

Kumari, Aruna; Dolly, J. Oliver; Ryan, Barry J.; Henehan, Gary

doi:10.1016/j.biocel.2014.07.013

Cited by 5 publications

(2 citation statements)

References 25 publications

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“…Both Ca 2+ and K + are essential for intestinal transport with regard to intracellular signaling and the maintenance of the membrane potential and changes in their transport may explain both the inhibition of glucose and alanine transport as well as the diverse effects of resveratrol on intracellular kinases in the different intestinal segments observed in the present study. Effects of RSV on Ca 2+ channels and signaling [ 44 , 45 ] and K + channels [ 46 , 47 ] have already been described in several studies. One link between the formation of AKAP/PKA signaling complexes and RSV may be the association of AKAPs and adenylate cyclase with lipid rafts [ 40 , 48 ] and the ability of RSV to influence the properties of bio membranes including lipid raft formation [ 33 , 34 , 35 ].…”

Section: Resultsmentioning

confidence: 99%

Resveratrol Inhibits Porcine Intestinal Glucose and Alanine Transport: Potential Roles of Na+/K+-ATPase Activity, Protein Kinase A, AMP-Activated Protein Kinase and the Association of Selected Nutrient Transport Proteins with Detergent Resistant Membranes

Klinger

Breves

2018

Nutrients

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Background: Beneficial effects of Resveratrol (RSV) have been demonstrated, including effects on transporters and channels. However, little is known about how RSV influences intestinal transport. The aim of this study was to further characterize the effects of RSV on intestinal transport and the respective mechanisms. Methods: Porcine jejunum and ileum were incubated with RSV (300 µM, 30 min) in Ussing chambers (functional studies) and tissue bathes (detection of protein expression, phosphorylation, association with detergent resistant membranes (DRMs)). Results: RSV reduced alanine and glucose-induced short circuit currents (ΔIsc) and influenced forskolin-induced ΔIsc. The phosphorylation of sodium–glucose-linked transporter 1 (SGLT1), AMP-activated protein kinase (AMPK), protein kinase A substrates (PKA-S) and liver kinase B1 (LKB1) increased but a causative relation to the inhibitory effects could not directly be established. The DRM association of SGLT1, peptide transporter 1 (PEPT1) and (phosphorylated) Na+/H+-exchanger 3 (NHE3) did not change. Conclusion: RSV influences the intestinal transport of glucose, alanine and chloride and is likely to affect other transport processes. As the effects of protein kinase activation vary between the intestinal localizations, it would appear that increasing cyclic adenosine monophosphate (cAMP) levels are part of the mechanism. Nonetheless, the physiological responses depend on cell type-specific structures.

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Section: Resultsmentioning

confidence: 99%

Resveratrol Inhibits Porcine Intestinal Glucose and Alanine Transport: Potential Roles of Na+/K+-ATPase Activity, Protein Kinase A, AMP-Activated Protein Kinase and the Association of Selected Nutrient Transport Proteins with Detergent Resistant Membranes

Klinger

Breves

2018

Nutrients

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“…Classical inhibitors of AKRs show very little inhibition of Kvβ-mediated catalysis, and currently, only a few pharmacological agents are known to impact Kvβ function; these act primarily as inhibitors of catalytic activity or by disrupting the association between the Kvβ and Kvα T1 docking domain. A recent study identified the acidic dopamine metabolite 3,4dihydroxphenylacetic acid (DOPAC) as an effective inhibitor of Kvβ2-mediated reduction of 4-nitrobenzaldehyde, inhibiting the production of 4-nitrobenzyl alcohol by ~40% [91], albeit at supraphysiological concentrations. Additional nonendogenous inhibitors such as the cardioprotective drug resveratrol and plant derived flavonoid rutin, only slightly inhibit Kvβ2 catalytic activity by ~38% each.…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

Biochemical and physiological properties of K+ channel-associated AKR6A (Kvβ) proteins

Raph

Bhatnagar

Nystoriak

2019

Chemico-Biological Interactions

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Voltage-gated potassium (Kv) channels play an essential role in the regulation of membrane excitability and thereby control physiological processes such as cardiac excitability, neural communication, muscle contraction, and hormone secretion. Members of the Kv1 and Kv4 families are known to associate with auxiliary intracellular Kvβ subunits, which belong to the aldo-keto reductase superfamily. Electrophysiological studies have shown that these proteins regulate the gating properties of Kv channels. Although the three gene products encoding Kvβ proteins are functional enzymes in that they catalyze the nicotinamide adenine dinucleotide phosphate (NAD[P]H)-dependent reduction of a wide range of aldehyde and ketone substrates, the physiological role for these proteins and how each subtype may perform unique roles in coupling membrane excitability with cellular metabolic processes remains unclear. Here, we discuss current knowledge of the enzymatic properties of Kvβ proteins from biochemical studies with their described and purported physiological and pathophysiological influences.

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Discovery of pyridoxal reductase activity as part of human vitamin B6 metabolism

Ramos

Albersen

Vringer

et al. 2019

Biochimica et Biophysica Acta (BBA) - General Subjects

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New inhibitors of the Kvβ2 subunit from mammalian Kv1 potassium channels

Cited by 5 publications

References 25 publications

Resveratrol Inhibits Porcine Intestinal Glucose and Alanine Transport: Potential Roles of Na+/K+-ATPase Activity, Protein Kinase A, AMP-Activated Protein Kinase and the Association of Selected Nutrient Transport Proteins with Detergent Resistant Membranes

Resveratrol Inhibits Porcine Intestinal Glucose and Alanine Transport: Potential Roles of Na+/K+-ATPase Activity, Protein Kinase A, AMP-Activated Protein Kinase and the Association of Selected Nutrient Transport Proteins with Detergent Resistant Membranes

Biochemical and physiological properties of K+ channel-associated AKR6A (Kvβ) proteins

Discovery of pyridoxal reductase activity as part of human vitamin B6 metabolism

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