Abstract Profilin 1 (PFN1) is an actin binding protein that vital for the polymerization of monomeric into filaments. Here we screened knockout cells novel functions PFN1 and discovered mitophagy, a type selective autophagy removes defective or damaged mitochondria from cell, was significantly upregulated in absence PFN1. Despite successful autophagosome formation fusion with lysosome, activation additional mitochondrial quality control pathways, still accumulate damaged, dysfunctional...

AngII (angiotensin II)-dependent hypertension causes comparable elevations of blood pressure (BP), aldosterone levels, and renal ENaC (epithelial Na+ channel) activity in male female rodents. Mineralocorticoid receptor (MR) antagonism has a limited antihypertensive effect associated with insufficient suppression rodents AngII-hypertension. While MR blockade effectively reduces BP mice salt-sensitive leptin-induced hypertension, not been studied We hypothesize that overstimulation signaling...

Regulation of cytoplasmic free calcium concentration [Ca(2+)]i is a key factor for the maintenance cellular homeostasis in different cell types, including lymphocytes. During T lymphocyte activation as well production cytokines, sustained Ca(2+) influx essential, however, it remains unclear how this regulated. Previously, we reported expression and functional activity channels TRPV5 TRPV6 (transient receptor potential vanilloid type 5 6) human leukemia Jurkat cells. In study, using single...

Angiotensin receptor blockers (ARBs) are the first-line treatment for hypertension; they act by inhibiting signaling through angiotensin 1 (AT1R). Recently, a novel biased AT1R agonist, TRV120027 (TRV), which selectively activates β-arrestin cascade and blocks G-protein-coupled pathway has been proposed as potential blood pressure medication. Here, we explored effects of TRV associated in podocytes, essential cells kidney filter. We used human podocyte cell lines to determine β-arrestin's...

Abstract The monomer-binding protein profilin 1 (PFN1) plays a crucial role in actin polymerization. However, mutations PFN1 are also linked to hereditary amyotrophic lateral sclerosis, resulting broad range of cellular pathologies which cannot be explained by its primary function as cytosolic assembly factor. This implies that there important, undiscovered roles for physiology. Here we screened knockout cells novel phenotypes associated with loss and discovered mitophagy was significantly...

Atrial Natriuretic Peptide (ANP) plays an important role in blood pressure regulation. Low levels of ANP correlate with the development salt-sensitive hypertension (SS-HTN). Our previous studies indicated that deficiency exacerbated renal function decline SS-HTN. In heart and fat tissue, was reported to affect lipid peroxidation mitochondrial bioenergetics but effects on kidney are unexplored. We hypothesized SS-HTN causes bioenergetic shift, leading disruption network oxidative stress. To...

cAMP is a universal second messenger regulating plethora of processes in the kidney. Two downstream effectors are PKA and exchange protein directly activated by (Epac), which, unlike PKA, often linked to elevation [Ca2+]i. While both Epac isoforms (Epac1 Epac2) expressed along nephron, their relevance kidney remains obscure. We combined ratiometric calcium imaging with quantitative immunoblotting, immunofluorescent confocal microscopy, balance studies mice lacking Epac1 or Epac2 determine...

Abstract Transient receptor potential vanilloid 6 (TRPV6) channels are key players in calcium metabolism of healthy and cancerous cells. Nevertheless, the mechanisms controlling abundance these plasma membrane cells to regulate Ca 2+ transport is still poorly understood. In this study, we provide first evidence that TRPV6 influx Jurkat T cell line modulated by cholesterol, a main lipid component membrane. Using patch‐clamp technique, found activity decreased cholesterol sequestration with...

Introduction: Nicotine consumption through vaping, cigarettes, or nicotine replacement therapy poses major risks for renal health, especially in individuals with hypertension kidney disease. induces oxidative stress and nitric oxide synthase (NOS) remodeling endothelial cells, but a gap knowledge persists regarding its impact on glomerular epithelial particularly podocytes. We hypothesize that promotes nitrosative podocytes, generating peroxynitrite (ONOO - ), causing mitochondrial damage,...

Introduction: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Most studies DKD are glomerulo-centric. The recent progress in control glucose handling by SGLT2i makes proximal tubule (PT) a prime candidate. Mitochondrial (mito) dysfunction and mito-induced oxidative stress well-studied known to accelerate tubular injury. Some have suggested role Atrial Natriuretic Peptide (ANP) DKD. ANP hormone that regulates salt/water homeostasis hemodynamics. We hypothesize...

Introduction: In general, renal disease susceptibility is higher in males than age-matched females until menopause. The damage to proximal tubules (PT) key the onset of kidney development due their high capacity for reabsorption and intense mitochondrial metabolism. Our previous data identified oxygen consumption cortex healthy male Sprague Dawley rats lower H 2 O production compared females. We hypothesize that sex differences substrate reliance trigger differential bioenergetic responses...

Preeclampsia (PE) affects 5-10% of pregnancies worldwide that increase maternal and fetal morbidity mortality. PE is often characterized by hypertension, endothelial dysfunction, restriction intrauterine growth. Our lab established mid-gestation leptin infusion in pregnant mice induces a model PE, notably reducing growth late gestation. Clinical studies indicate patients demonstrate elevated levels compared to healthy as well present with evidence placental mitochondrial dysfunction....

Introduction. Aging is accompanied by changes in multiple factors, such as accumulation of mitochondrial dysfunction and the decline sex hormone levels throughout life. Females are generally protected from renal diseases until menopause, potentially a result presence female hormones. Sex hormones govern plethora crucial processes, including metabolism bioenergetics. However, there remains gap knowledge regarding role bioenergetics aging. We hypothesized this study that removal will...

INTRODUCTION. Lithium (Li + ) is an effective mood stabilizer that continues to be widely used in modern psychiatric practice. One of the most common adverse effects Li therapy nephrogenic diabetes insipidus manifesting reduced urinary concentrating ability due impaired vasopressin (AVP) signaling collecting duct principal cells. While distal tubular acidosis has also been reported patients receiving , molecular determinants underlying pathophysiological on intercalated cells and renal...

Background. Histamine is a nitrogen-based molecule that has established involvement in allergic reactions and immune responses. The levels of histamine are increased renal pathologies, such as nephrotic syndrome, diabetic nephropathy, acute failure, end stage kidney disease. We have previously shown all 4 receptors (HR1 to HR4) abundant the kidney, exposure can affect intracellular Ca 2+ collecting ducts. Calcium signaling an important regulator actin cytoskeleton dynamics these cells, thus,...

Introduction: Although nicotine’s harmful effects on renal function are established, the precise cellular mechanisms of smoking-related damage understudied. Smoking-Related Glomerulopathy (SRG) is a disease phenotype associated with smoking. This condition histologically mimics diabetic nephropathy, however, SRG patients present proteinuria and insufficiency without diabetes. Here we investigated acute chronic nicotine-related oxidative nitrosative stress in glomerular podocytes. We...

INTRODUCTION. Lithium salts are used as mood stabilizers to treat bipolar disorder and depression. A common renal side effect of lithium therapy is nephrogenic diabetes insipidus (NDI), manifesting in polyuria. decreases the numbers aquaporin 2 (AQP2) water channels collecting duct cells reducing reabsorption response vasopressin (AVP). Stimulation purinergic P2Y2 receptors (P2Y2R) can impair AVP signaling deletion P2Y2R mice slows down progression lithium-induced NDI. Interestingly,...

INTRODUCTION. Hypertension remains a major public health problem, affecting nearly half of the adults in USA. In most cases there is no readily identifiable cause and hypertension referred to as essential. Spontaneously hypertensive rat (SHR) model essential hypertension. The existing data on mechanisms underlying blood pressure (BP) increase SHR are often contradictory, yet some studies indicate that BP elevation dependent mineralocorticoid, aldosterone, positively correlates with...

Red blood cell (RBC) trapping presents as the expansion of- and obstruction, of outer-medullary capillaries kidney with tightly packed RBCs. RBC has been thought to promote hypoxic tubular injury by extending ischemia time outer-medulla. Recent evidence from our laboratory; however, indicates that may toxic injury, secondary mitochondrial uptake iron hemoglobin released damaged RBCs in nearby congested capillaries. In current study, we tested hypothesis ‘RBC promotes dysfunction independent...

Background. Inflammation is one of the key mechanisms for development salt-sensitive hypertension (SS-HTN) and damage to kidney. We have previously reported that kidneys express components histaminergic system, are capable local production histamine, a well-known inflammatory mediator. showed renal histamine level increased in SS-HTN. Histamine content tightly regulated by enzyme histamine-N-methyltransferase, which has higher abundance kidney compared other organs. hypothesized an...

Introduction. In 2020, more than 670,000 deaths in the United States had hypertension as a primary or contributing cause. Females generally exhibit less susceptibility to hypertensive renal damage compared males. It is established that mitochondrial dysfunction and associated oxidative stress contribute development. Our previous studies have shown healthy mitochondria absence of sex differences antioxidant protein abundance, ROS production, oxygen consumption rates. We hypothesized here...