Involvement of ADAM17-Klotho Crosstalk in High Glucose-Induced Alterations of Podocyte Function.

Microalbuminuria is the earliest clinical abnormality in diabetic kidney disease. High glucose (HG) concentrations are associated with the induction of oxidative stress in podocytes, leading to disruption of the glomerular filtration barrier. Our recent study revealed a significant decrease in the membrane-bound fraction of Klotho in podocytes that were cultured under HG conditions.

Biological Evaluation of a Rhodium(III) Bipyridylsulfonamide Complex: Effects on Mitochondrial Dynamics and Cytoskeletal Remodeling in Breast Cancer Cells.

Rhodium(III) complexes have gained attention for their anticancer potential. In this study, we investigated a rhodium(III) bipyridylsulfonamide complex () and its ligand () for their effects on breast cancer (SKBr3) and noncancerous mammary cells (HB2). Both compounds significantly reduced oxidative phosphorylation (OXPHOS) and mitochondrial function in SKBr3 cells while sparing HB2 cells.

Polymers of functionalized diaminopropionic acid are efficient mediators of active exogenous enzyme delivery into cells.

Delivery of active protein especially enzyme is one of the major therapeutic challenge. Replacing or substituted invalid/improper acting protein offer fast and effective treatment of disease. Herein, we describe the synthesis and properties of biotinylated peptidomimetics consisting of oxoacid-modified 2,3, L-diaminopropionic acid residues with guanidine groups on its side chains.

ADAM10 as a major activator of reactive oxygen species production and klotho shedding in podocytes under diabetic conditions.

Early stages of diabetes are characterized by elevations of insulin and glucose concentrations. Both factors stimulate reactive oxygen species (ROS) production, leading to impairments in podocyte function and disruption of the glomerular filtration barrier. Podocytes were recently shown to be an important source of αKlotho (αKL) expression.

Lactate regulates respiratory efficiency and mitochondrial dynamics in primary rat podocytes.

Podocytes are crucial for regulating glomerular permeability. They have foot processes that are integral to the renal filtration barrier. Understanding their energy metabolism could shed light on the pathogenesis of filtration barrier injury.

Insulin induces bioenergetic changes and alters mitochondrial dynamics in podocytes.

Diabetic nephropathy (DN) is one of the most frequent complications of diabetes. Early stages of DN are associated with hyperinsulinemia and progressive insulin resistance in insulin-sensitive cells, including podocytes. The diabetic environment induces pathological changes, especially in podocyte bioenergetics, which is tightly linked with mitochondrial dynamics.

Optimization of fluorescent substrates for ADAM17 and their utility in the detection of diabetes.

ADAM17 (a disintegrin and metalloproteinase 17) is a sheddase that releases various types of membrane-associated proteins, including adhesive molecules, cytokines and their receptors, and inflammatory mediators. Evidence suggests that the enzyme is involved in the proteolytic cleavage of antiaging transmembrane protein Klotho (KL). What is more, reduced serum and urinary KL levels are observed in the early stages of chronic kidney disease.

Role of lysosomes in insulin signaling and glucose uptake in cultured rat podocytes.

Podocytes are sensitive to insulin, which governs the functional and structural integrity of podocytes that are essential for proper function of the glomerular filtration barrier. Lysosomes are acidic organelles that are implicated in regulation of the insulin signaling pathway. Cathepsin D (CTPD) and lysosome-associated membrane protein 1 (LAMP1) are major lysosomal proteins that reflect the functional state of lysosomes.

Initial study of the detection of ADAM 10 in the urine of type-2 diabetic patients.

Diabetes mellitus (DM) is a disease of civilization. If left untreated, it can cause serious complications and significantly shortens the life time. DM is one of the leading causes of end-stage renal disease (uremia) worldwide.

Pit 1 transporter (SLC20A1) as a key factor in the NPP1-mediated inhibition of insulin signaling in human podocytes.

Podocytes are crucially involved in blood filtration in the glomerulus. Their proper function relies on efficient insulin responsiveness. The insulin resistance of podocytes, defined as a reduction of cell sensitivity to this hormone, is the earliest pathomechanism of microalbuminuria that is observed in metabolic syndrome and diabetic nephropathy.

The Role of PKGIα and AMPK Signaling Interplay in the Regulation of Albumin Permeability in Cultured Rat Podocytes.

The permeability of the glomerular filtration barrier (GFB) is mainly regulated by podocytes and their foot processes. Protein kinase G type Iα (PKGIα) and adenosine monophosphate-dependent kinase (AMPK) affect the contractile apparatus of podocytes and influence the permeability of the GFB. Therefore, we studied the interplay between PKGIα and AMPK in cultured rat podocytes.

Role of L-lactate as an energy substrate in primary rat podocytes under physiological and glucose deprivation conditions.

Lactate has long been acknowledged to be a metabolic waste product, but it has more recently been found as a fuel energy source in mammalian cells. Podocytes are an important component of the glomerular filter, and their role in maintaining the structural integrity of this structure was established. These cells rely on a constant energy supply and reservoir.

Inhibition of phosphodiesterase 5A by tadalafil improves SIRT1 expression and activity in insulin-resistant podocytes.

A decrease in intracellular levels of 3',5'-cyclic guanosine monophosphate (cGMP) has been implicated in the progression of diabetic nephropathy. Hyperglycemia significantly inhibits cGMP-dependent pathway activity in the kidney, leading to glomerular damage and proteinuria. The enhancement of activity of this pathway that is associated with an elevation of cGMP levels may be achieved by inhibition of the cGMP specific phosphodiesterase 5A (PDE5A) using selective inhibitors, such as tadalafil.

β-Aminoisobutyric acid (L-BAIBA) is a novel regulator of mitochondrial biogenesis and respiratory function in human podocytes.

Podocytes constitute an external layer of the glomerular filtration barrier, injury to which is a hallmark of renal disease. Mitochondrial dysfunction often accompanies podocyte damage and is associated with an increase in oxidative stress and apoptosis. β-Aminoisobutyric acid (BAIBA) belongs to natural β-amino acids and is known to exert anti-inflammatory and antioxidant effects.

Enhancement of cGMP-dependent pathway activity ameliorates hyperglycemia-induced decrease in SIRT1-AMPK activity in podocytes: Impact on glucose uptake and podocyte function.

Hyperglycemia significantly decreases 3',5'-cyclic guanosine monophosphate (cGMP)-dependent pathway activity in the kidney. A well-characterized downstream signaling effector of cGMP is cGMP-dependent protein kinase G (PKG), exerting a wide range of downstream effects, including vasodilation and vascular smooth muscle cells relaxation. In podocytes that are exposed to high glucose concentrations, crosstalk between the protein deacetylase sirtuin 1 (SIRT1) and adenosine monophosphate-dependent protein kinase (AMPK) decreased, attenuating insulin responsiveness and impairing podocyte function.

Insights into the regulation of podocyte and glomerular function by lactate and its metabolic sensor G-protein-coupled receptor 81.

Podocytes and their foot processes are an important cellular layer of the renal filtration barrier that is involved in regulating glomerular permeability. Disturbances of podocyte function play a central role in the development of proteinuria in diabetic nephropathy. The retraction and effacement of podocyte foot processes that form slit diaphragms are a common feature of proteinuria.

Insulin controls cytoskeleton reorganization and filtration barrier permeability via the PKGIα-Rac1-RhoA crosstalk in cultured rat podocytes.

Podocyte foot processes are an important cellular layer of the glomerular barrier that regulates glomerular permeability. Insulin via the protein kinase G type Iα (PKGIα) signaling pathway regulates the balance between contractility and relaxation (permeability) of the podocyte barrier by regulation of the actin cytoskeleton. This mechanism was shown to be disrupted in diabetes.

Novel Markers in Diabetic Kidney Disease-Current State and Perspectives.

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease. Along with the increasing prevalence of diabetes, DKD is expected to affect a higher number of patients. Despite the major progress in the therapy of DKD and diabetes mellitus (DM), the classic clinical diagnostic tools in DKD remain insufficient, delaying proper diagnosis and therapeutic interventions.

PTEN-induced kinase 1 deficiency alters albumin permeability and insulin signaling in podocytes.

Alterations of insulin signaling in diabetes are associated with podocyte injury, proteinuria, and renal failure. Insulin stimulates glucose transport to cells and regulates other intracellular processes that are linked to cellular bioenergetics, such as autophagy, gluconeogenesis, fatty acid metabolism, and mitochondrial homeostasis. The dysfunction of mitochondrial dynamics, including mitochondrial fusion, fission, and mitophagy, has been observed in high glucose-treated podocytes and renal cells from patients with diabetes.

Hyperglycemic environment disrupts phosphate transporter function and promotes calcification processes in podocytes and isolated glomeruli.

Soft tissue calcification is a pathological phenomenon that often occurs in end-stage chronic kidney disease (CKD), which is caused by diabetic nephropathy, among other factors. Hyperphosphatemia present during course of CKD contributes to impairments in kidney function, particularly damages in the glomerular filtration barrier (GFB). Essential elements of the GFB include glomerular epithelial cells, called podocytes.

Purinergic P2 receptors: Involvement and therapeutic implications in diabetes-related glomerular injury.

The purinergic activation of P2 receptors initiates a powerful and rapid signaling cascade that contributes to the regulation of an array of physiological and pathophysiological processes in many organs, including the kidney. P2 receptors are broadly distributed in both epithelial and vascular renal cells. Disturbances of purinergic signaling can lead to impairments in renal function.

Analysis of urinary kallikrein-related peptidase 13 for monitoring bladder cancer.

Background: Bladder cancer (BC) is one of the 10 most common types of cancer worldwide, with approximately 550,000 new cases each year. Early detection and appropriate diagnosis are important factors in successful treatment of the disease.

Material And Methods: We used specific fluorogenic substrate for the quantitative determination of urine kallikrein 13 (KLK13) activity in healthy ( = 15) and BC ( = 54) patients.

Hyperglycemia alters mitochondrial respiration efficiency and mitophagy in human podocytes.

Podocytes constitute the outer layer of the renal glomerular filtration barrier. Their energy requirements strongly depend on efficient oxidative respiration, which is tightly connected with mitochondrial dynamics. We hypothesized that hyperglycemia modulates energy metabolism in glomeruli and podocytes and contributes to the development of diabetic kidney disease.

Role of Klotho in Hyperglycemia: Its Levels and Effects on Fibroblast Growth Factor Receptors, Glycolysis, and Glomerular Filtration.

Hyperglycemic conditions (HG), at early stages of diabetic nephropathy (DN), cause a decrease in podocyte numbers and an aberration of their function as key cells for glomerular plasma filtration. Klotho protein was shown to overcome some negative effects of hyperglycemia. Klotho is also a coreceptor for fibroblast growth factor receptors (FGFRs), the signaling of which, together with a proper rate of glycolysis in podocytes, is needed for a proper function of the glomerular filtration barrier.

Beneficial effects of metformin on glomerular podocytes in diabetes.

Podocytes and their foot processes form an important cellular layer of the glomerular barrier involved in regulating glomerular permeability. Disturbances in podocyte function play a central role in the development of proteinuria in diabetic nephropathy. The retraction of podocyte foot processes forming a slit diaphragm is a common feature of proteinuria.