A Case of Reverse McConnell's Sign Associated With Acute Respiratory Distress Syndrome and Septic Shock.

We present a case of reverse McConnell's sign, a rare echocardiographic finding of right ventricular apical hypokinesis and basal hyperkinesis, in a patient with acute respiratory distress syndrome and septic shock. Although multiple etiologies were hypothesized, providers attributed this cardiomyopathy to increased right heart afterload from hypoxic pulmonary vasoconstriction. Cardiac function normalized as the patient's respiratory failure and sepsis resolved.

Cardiac Oxidative Signaling and Physiological Hypertrophy in the Na/K-ATPase α1α2 Mouse Model of High Affinity for Cardiotonic Steroids.

The Na/K-ATPase is the specific receptor for cardiotonic steroids (CTS) such as ouabain and digoxin. At pharmacological concentrations used in the treatment of cardiac conditions, CTS inhibit the ion-pumping function of Na/K-ATPase. At much lower concentrations, in the range of those reported for endogenous CTS in the blood, they stimulate hypertrophic growth of cultured cardiac myocytes through initiation of a Na/K-ATPase-mediated and reactive oxygen species (ROS)-dependent signaling.

The Na/K-ATPase α1/Src interaction regulates metabolic reserve and Western diet intolerance.

Aim: Highly prevalent diseases such as insulin resistance and heart failure are characterized by reduced metabolic flexibility and reserve. We tested whether Na/K-ATPase (NKA)-mediated regulation of Src kinase, which requires two NKA sequences specific to the α1 isoform, is a regulator of metabolic capacity that can be targeted pharmacologically.

Methods: Metabolic capacity was challenged functionally by Seahorse metabolic flux analyses and glucose deprivation in LLC-PK1-derived cells expressing Src binding rat NKA α1, non-Src-binding rat NKA α2 (the most abundant NKA isoform in the skeletal muscle), and Src binding gain-of-function mutant rat NKA α2.

Biased Effect of Cardiotonic Steroids on Na/K-ATPase-Mediated Signal Transduction.

Recent studies have revealed that Na/K-ATPase (NKA) can transmit signals through ion-pumping-independent activation of pathways relayed by distinct intracellular protein/lipid kinases, and endocytosis challenges the traditional definition that cardiotonic steroids (CTS) are NKA inhibitors. Although additional effects of CTS have long been suspected, revealing its agonist impact through the NKA receptor could be a novel mechanism in understanding the basic biology of NKA. In this study, we tested whether different structural CTS could trigger different sets of NKA/effector interactions, resulting in biased signaling responses without compromising ion-pumping capacity.

A caveolin binding motif in Na/K-ATPase is required for stem cell differentiation and organogenesis in mammals and .

Several signaling events have been recognized as essential for regulating cell lineage specification and organogenesis in animals. We find that the gain of an amino-terminal caveolin binding motif (CBM) in the α subunit of the Na/K-adenosine triphosphatase (ATPase) (NKA) is required for the early stages of organogenesis in both mice and . The evolutionary gain of the CBM occurred at the same time as the acquisition of the binding sites for Na/K.

Na/K-ATPase/src complex mediates regulation of CD40 in renal parenchyma.

Background: Recent studies have highlighted a critical role for CD40 in the pathogenesis of renal injury and fibrosis. However, little is currently understood about the regulation of CD40 in this setting.

Methods: We use novel Na/K-ATPase cell lines and inhibitors in order to demonstrate the regulatory function of Na/K-ATPase with regards to CD40 expression and function.

Circulating CD40 and sCD40L Predict Changes in Renal Function in Subjects with Chronic Kidney Disease.

Soluble CD40 ligand (sCD40L) has been implicated in the development of renal injury. The CD40 receptor exists in a soluble form, sCD40R, and has been shown to function as a competitive antagonist against CD40 activation. We analyzed whether plasma levels of sCD40L and sCD40R predict changes in renal function in an all-cause chronic kidney disease (CKD) cohort.

MicroRNA profiling in kidney disease: Plasma versus plasma-derived exosomes.

Liquid biopsies have advanced rapidly in recent years for use in diagnostic and prognostic applications. One important aspect of this advancement is the growth in our understanding of microRNA (miRNA) biology. The measurement of miRNAs packaged within exosomes, which are constantly released into the blood stream, may reflect pathological changes within the body.

Cigarette smoking causes epigenetic changes associated with cardiorenal fibrosis.

Clinical studies indicate that smoking combustible cigarettes promotes progression of renal and cardiac injury, leading to functional decline in the setting of chronic kidney disease (CKD). However, basic studies using in vivo small animal models that mimic clinical pathology of CKD are lacking. To address this issue, we evaluated renal and cardiac injury progression and functional changes induced by 4 wk of daily combustible cigarette smoke exposure in the 5/6th partial nephrectomy (PNx) CKD model.

Na/K-ATPase signaling regulates collagen synthesis through microRNA-29b-3p in cardiac fibroblasts.

Chronic kidney disease (CKD) is accompanied by cardiac fibrosis, hypertrophy, and dysfunction, which are commonly referred to as uremic cardiomyopathy. Our previous studies found that Na/K-ATPase ligands or 5/6th partial nephrectomy (PNx) induces cardiac fibrosis in rats and mice. The current study used in vitro and in vivo models to explore novel roles for microRNA in this mechanism of cardiac fibrosis formation.

Involvement of Na/K-ATPase in hydrogen peroxide-induced activation of the Src/ERK pathway in LLC-PK1 cells.

We have shown that Na/K-ATPase interacts with Src. Here, we test the role of this interaction in H2O2-induced activation of Src and ERK. We found that exposure of LLC-PK1 cells to H2O2 generated by the addition of glucose oxidase into the culture medium activated Src and ERK1/2.

Regulation of renal function and structure by the signaling Na/K-ATPase.

The Na/K-ATPase as an essential ion pump was discovered more than 50 years ago (Skou (1989) Biochim. Biophys. Acta 1000, 439-446; Feraille and Doucet (2001) Physiol.

Identification of a potential receptor that couples ion transport to protein kinase activity.

In our previous studies, we have demonstrated that the Src-coupled α1 Na/K-ATPase works as a receptor for cardiotonic steroids, such as ouabain, to regulate cellular protein kinase cascades. Here, we explore further the structural determinants of the interaction between the α1 Na/K-ATPase and Src and demonstrate that the Src-coupled α1 Na/K-ATPase allows the cell to decode the transmembrane transport activity of the Na/K-ATPase to turn on/off protein kinases. The α1 Na/K-ATPase undergoes E1/E2 conformational transition during an ion pumping cycle.