A5031871282- Ion channel regulation and function
- Ion Transport and Channel Regulation
- Cardiac electrophysiology and arrhythmias
- Pancreatic function and diabetes
- Magnesium in Health and Disease
- Diabetes and associated disorders
- Neuroscience and Neuropharmacology Research
- Parathyroid Disorders and Treatments
- Amino Acid Enzymes and Metabolism
- Parvovirus B19 Infection Studies
- Endoplasmic Reticulum Stress and Disease
- Diet, Metabolism, and Disease
- Prenatal Screening and Diagnostics
- RNA Research and Splicing
- Erythrocyte Function and Pathophysiology
- Metabolism, Diabetes, and Cancer
- Genetic Syndromes and Imprinting
- Ion Channels and Receptors
- RNA Interference and Gene Delivery
- Caveolin-1 and cellular processes
- Receptor Mechanisms and Signaling
- MicroRNA in disease regulation
- Phagocytosis and Immune Regulation
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Biomedical Research and Pathophysiology
Université Libre de Bruxelles
2021-2022
University College London
2021
University of Tübingen
2013-2017
Background/Aims: Human parvovirus B19 (B19V) may cause inflammatory cardiomyopathy (iCMP) which is accompanied by endothelial dysfunction. The B19V capsid protein VP1 contains a lysophosphatidylcholine producing phospholipase A2 (PLA) sequence. Lysophosphatidylcholine has in turn been shown to inhibit Na+/K+ ATPase. present study explored whether modifies ATPase activity. Methods:Xenopus oocytes were injected with cRNA encoding isolated from patient suffering fatal B19V-iCMP or PLA2-negative...
<b><i>Background/Aims: </i></b>Klotho, a protein mainly produced in the kidney and released into circulating blood, contributes to negative regulation of 1,25(OH)<sub>2</sub>D<sub>3</sub> formation is thus powerful regulator mineral metabolism. As β-glucuronidase, alpha Klotho further regulates stability several carriers channels plasma membrane channel transporter activity. Accordingly, participates diverse functions seemingly unrelated...
<b><i>Background/Aims: </i></b>The transmembrane Klotho protein contributes to inhibition of 1,25(OH)<sub>2</sub>D<sub>3</sub> formation. The extracellular domain could function as an enzyme with e.g. β-glucuronidase activity, be cleaved off and released into blood cerebrospinal fluid. regulates several cellular transporters. deficiency accelerates the appearance age related disorders including neurodegeneration muscle wasting eventually leads...
Type 1 diabetes (T1D) results from autoimmune destruction of β-cells in the pancreas. Protein tyrosine phosphatases (PTPs) are candidate genes for T1D and play a key role disease development β-cell dysfunction. Here, we assessed global protein individual PTP profiles pancreas nonobese mice with early-onset (NOD) treated an anti-CD3 monoclonal antibody interleukin-1 receptor antagonist. The treatment reversed hyperglycemia, observed enhanced expression PTPN2, family member gene, endoplasmic...
Thioredoxin-interacting protein (TXNIP) plays a role in regulating endoplasmic reticulum (ER) and oxidative stress, which disrupt glucose homeostasis diabetes. However, the impact of TXNIP deficiency on differentiation functionality human stem cell-derived somatic metabolic cells remains unclear. We used CRISPR-Cas12a genome editing to generate TXNIP-deficient (TXNIP-/-) H1 embryonic (H1-hESCs). These were differentiated into hepatocyte-like (HLCs) stem-cell-derived insulin-producing islets...
<b><i>Background/Aims: </i></b>Transport regulation involves several kinases including SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1), which are under control of WNK (with-no-K[Lys]) kinases. The present study explored whether and/or participate in the creatine transporter CreaT (SLC6A8), accomplishes Na<sup>+</sup> coupled cellular uptake tissues kidney, intestine, heart, skeletal muscle brain....
<b><i>Background/Aims: </i></b>SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1) are powerful regulators of diverse transport processes. Both kinases activated by cell shrinkage participate in stimulation regulatory volume increase (RVI). Execution RVI involves inhibition Cl<sup>-</sup> channels. The present study explored whether SPAK and/or regulate the activity channel ClC-2. <b><i>Methods:...
SPAK (STE20-related proline/alanine-rich kinase) is a powerful regulator of renal tubular ion transport and blood pressure. Moreover, contributes to the regulation cell volume. Little known, however, about role in or organic solutes. The present study thus addressed influence on peptide transporters PEPT1 PEPT2.To this end, cRNA encoding PEPT2 were injected into Xenopus laevis oocytes without with additional injection wild-type, SPAK, WNK1 insensitive inactive (T233A)SPAK, constitutively...
<b><i>Background/Aims: </i></b>OSR1 (oxidative-stress-responsive kinase 1) participates in the regulation of renal tubular ion transport, cell volume and blood pressure. Whether OSR1 contributes to organic solute transport remained; however, elusive. The present study thus explored sensitivity peptide transporters PEPT1 PEPT2. <b><i>Methods: </i></b>cRNA encoding or PEPT2 were injected into <i>Xenopus</i> oocytes without with...
<b><i>Background/Aims: </i></b>The kinases SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1) participate in the regulation of NaCl cotransporter NCC Na<sup>+</sup>,K<sup>+</sup>,2Cl<sup>-</sup> NKCC2. The are regulated by WNK (with-no-K[Lys]) kinases. Mutations genes encoding underly Gordon's syndrome, a monogenic disease leading to hypertension hyperkalemia. further regulate renal outer...
<b><i>Background/Aims: </i></b>Renal tissue fibrosis contributes to the development of end-stage renal disease. Causes for include obstructive nephropathy. The following unilateral ureteral obstruction (UUO) is blunted in gene-targeted mice lacking functional serum- and glucocorticoid-inducible kinase SGK1. Similar Akt isoforms, SGK1 phosphorylates thus inactivates glycogen synthase GSK-3. present study explored whether PKB/SGK-dependent phoshorylation GSK-3α/β...
Gene variants of the leucine-rich repeat kinase 2 (LRRK2) are associated with susceptibility to Parkinson's disease (PD). Besides brain and periphery, LRRK2 is expressed in various immune cells including dendritic (DCs), antigen-presenting linking innate adaptive immunity. However, function system still incompletely understood. Here, Ca2+-signaling was analyzed DCs isolated from gene-targeted mice lacking lrrk2 (Lrrk2-/-) their wild-type littermates (Lrrk2). According Western blotting, Lrrk2...
<b><i>Background/Aims: </i></b>The WNK-dependent STE20/SPS1-related proline/alanine-rich kinase SPAK participates in the regulation of NaCl and Na<sup>+</sup>,K<sup>+</sup>,2Cl<sup>-</sup> cotransport thus renal salt excretion. The present study explored whether has similarly potential to regulate epithelial Na<sup>+</sup> channel (ENaC). <b><i>Methods: </i></b>ENaC was expressed...
Background/Aims: The serum & glucocorticoid inducible kinase SGK3, an ubiquitously expressed serine/threonine kinase, regulates a variety of ion channels. It has previously been shown that SGK3 upregulates the outwardly rectifying K+ channel KV11.1, which is in cardiomyocytes. Cardiomyocytes further express inward rectifier Kir2.1, contributes to maintenance resting cell membrane potential. Loss-of-function mutations KCNJ2 encoding Kir2.1 result Andersen-Tawil syndrome with periodic...
CD44 is required for signalling of macrophage migration inhibitory factor (MIF), an anti-apoptotic pro-inflammatory cytokine. MIF expressed and released from blood platelets, key players in the orchestration occlusive vascular disease. Nothing known about a role regulation platelet function. The present study thus explored whether modifies degranulation (P-selectin exposure), integrin activation, caspase activity, phosphatidylserine exposure on surface, volume, Orai1 protein abundance...
Most obese and insulin-resistant individuals do not develop diabetes. This is the result of capacity β-cells to adapt produce enough insulin cover needs organism. The underlying mechanism β-cell adaptation in obesity, however, remains unclear. Previous studies have suggested a role for STAT3 mediating development human glucose homeostasis, but little known about obesity. We observed enhanced cytoplasmic expression severely subjects with To address functional adult β-cells, we generated mice...
Background/Aims: Janus kinase 3 (JAK3), a tyrosine contributing to the regulation of cell proliferation and apoptosis lymphocytes tumour cells, has been shown modify expression function several ion channels transport proteins. Channels involved in include large conductance voltage- Ca2+-activated K+ channel BK. The present study explored whether JAK3 modifies BK protein abundance current. Methods: cRNA encoding Ca2+-insensitive (BKM513I+Δ899-903) was injected into Xenopus oocytes with or...
Klotho is a transmembrane protein expressed primarily in kidney, parathyroid gland, and choroid plexus. The extracellular domain could be cleaved off released into the systemic circulation. part effective as β-glucuronidase regulating stability cell membrane. major determinant of aging life span. Overexpression increases deficiency decreases may further result hearing loss cardiac arrhythmia. present study explored whether modifies activity abundance KCNQ1/KCNE1, K+ channel required for...
<b><i>Background/Aims: </i></b>SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1), kinases controlled by WNK (with-no-K[Lys] kinase), are powerful regulators of cellular ion transport blood pressure. Observations in gene-targeted mice disclosed an impact SPAK/OSR1 on phosphate metabolism. The present study thus tested whether SPAK and/or contributes to the regulation intestinal Na<sup>+</sup>-coupled...
Background/Aims: KCNQ1/E1 channels are expressed in diverse tissues and serve a variety of functions including endolymph secretion the inner ear, cardiac repolarization, epithelial transport cell volume regulation. Kinases involved regulation include SPAK (SPS1-related proline/alanine-rich kinase) OSR1 (oxidative stress-responsive kinase 1), which under control WNK (with-no-K[Lys]) kinases. The present study explored whether regulated by and/or OSR1. Methods: cRNA encoding was injected into...