Biomedical subjects

N Anilkumar

Publications and source records attributed to N Anilkumar.

6 recordsLinked to original sources

PubMed2006

Redox signalling involving NADPH oxidase-derived reactive oxygen species.

Increased oxidative stress plays an important role in the pathophysiology of many diseases such as atherosclerosis, diabetes mellitus, myocardial infarction and heart failure. In addition to the well-known damaging effects of oxygen-free radicals, ROS (reactive oxygen species) also have signalling roles, acting as second messengers that modulate the activity of diverse intracellular signalling pathways and transcription factors, thereby inducing changes in cell phenotype. NADPH oxidases appear to be especially important sources of ROS involved in redox signalling. Seven NADPH oxidase isoforms, known as Noxs (NAPDH oxidases), are expressed in a cell- and tissue-specific fashion. These oxidases are thought to subserve distinct functions as a result of their tightly regulated activation (e.g. by neurohormonal and growth factors and mechanical stimuli) and their specific coupling with distinct downstream signalling pathways. In the present paper, we review the structure and mechanisms of activation of NADPH oxidases and consider their involvement in redox signalling, focusing mainly on the cardiovascular system.

Atherosclerosis↗

PubMed2003

Interaction of fascin and protein kinase Calpha: a novel intersection in cell adhesion and motility.

Coordination of protrusive and contractile cell-matrix contacts is important for cell adhesion and migration, but the mechanisms involved are not well understood. We report an unexpected direct association between fascin, an actin-bundling component of filopodia, microspikes and lamellipodial ribs, and protein kinase Calpha (PKCalpha), a regulator of focal adhesions. The association is detectable by protein-protein binding in vitro, by coimmunoprecipitation from cell extracts, and in live cells as fluorescence resonance energy transfer detected by fluorescence imaging lifetime microscopy. The interaction is physiologically regulated by the extracellular matrix context of cells, depends on activation of PKCalpha and is mediated by the C1B domain of PKCalpha. Strikingly, a fascin mutant, fascin S39D, associates constitutively with PKCalpha. Through use of a newly developed set of membrane-permeable peptides that separately inhibit either fascin/PKCalpha or fascin/actin binding, we have uncovered that specific blockade of the fascin/PKCalpha interaction increases cell migration on fibronectin in conjunction with increased fascin protrusions and remodeling of focal adhesions. These results identify the fascin-PKCalpha interaction as an important novel intersection in the regulation and networking of cell-matrix contacts.

Animals↗

PubMed2002

Fascins, and their roles in cell structure and function.

The fascins are a structurally unique and evolutionarily conserved group of actin cross-linking proteins. Fascins function in the organisation of two major forms of actin-based structures: dynamic, cortical cell protrusions and cytoplasmic microfilament bundles. The cortical structures, which include filopodia, spikes, lamellipodial ribs, oocyte microvilli and the dendrites of dendritic cells, have roles in cell-matrix adhesion, cell interactions and cell migration, whereas the cytoplasmic actin bundles appear to participate in cell architecture. We discuss the current understanding of the cellular mechanisms that regulate the binding of fascin to actin and how these processes contribute to the organisation or disassembly of cell protrusions. Although the in vivo roles of fascin have been studied principally in Drosophila, several human diseases are associated with inherited or acquired alterations in the expression of fascins. Strategies to modulate fascin-containing protrusions and thereby cell adhesive and migratory behaviour could have potential for therapeutic intervention in these conditions. The supplementary material referred to in this section can be found at http://www.interscience.wiley.com/jpages/0265-9247/suppmat/2002/v24.350.html

Actins↗

PubMed1996

Modulation of alpha 5 beta 1 and alpha V beta 3 integrins on the cell surface during mitosis.

One of the hallmarks of cells undergoing mitotic division is their rounded morphology and reduced adhesion to the substratum. We have studied and compared the attachment of interphase and mitotic cells to substrata coated with fibronectin and vitronectin. We have found that adhesion of mitotic cells, as compared to interphase cells, is significantly reduced to fibronectin, but is higher to vitronectin. These results correlate well with the expression of alpha 5 beta 1 and alpha V beta 3 integrins, the respective receptors for fibronectin and vitronectin, on the cell surface. Mitotic cells show higher levels of alpha V beta 3 and very low levels of alpha 5 beta 1 proteins on the cell surface as compared to interphase cells. This difference in the levels of these integrins also reflects in the total amounts of fibronectin and vitronectin present on the cell surface of these cells. We have further shown, by flow cytometry, that binding of vitronectin, or the synthetic peptide -GRGDSP-, causes an increase in the intracellular levels of Ca2+ in mitotic cells, but no change is seen in the interphase cells. Binding of fibronectin to either of these cells fails to elicit any response. One interesting feature of our results is that the levels of total, i.e., cytoplasmic plus membrane bound, alpha 5 beta 1 and alpha V beta 3 integrins of mitotic and interphase cells remain the same, thus implying an alteration in the distribution of integrin chains between the plasma membrane and the cytoplasm during the conversion of interphase cells into the mitotic phase.

Animals↗

PubMed1993

Isolation and characterization of laminin binding protein from regenerating rat liver plasma membrane.

Interaction of rat hepatocytes with laminin, the major basement membrane adhesive glycoprotein was studied. Rat fetal hepatocytes attached more to laminin than adult hepatocytes. Laminin promoted attachment of fetal hepatocytes in a concentration dependent manner and showed saturable binding pattern. Hepatocytes from CCl4 induced regenerating rat liver also attached more to laminin. The pentapeptide YIGSR derived from laminin promoted attachment of adult and fetal hepatocytes, but to a lesser extent. A 67 kDa protein was isolated from the hepatic plasma membrane of CCl4 induced regenerating rat liver by affinity chromatography over laminin sepharose. This protein appeared to be relatively abundant in regenerating liver than in normal liver. The radioiodinated 67 kDa protein could be inserted into liposomes and these liposomes attached to coverslips coated with laminin in a concentration dependent manner in a divalent cation free medium. Its specificity for laminin was also revealed by absence of significant binding to fibronectin and collagen.

Amino Acid Sequence↗

PubMedDate not supplied

An echocardiographic study of net atrioventricular compliance in juvenile and adult mitral stenosis.

BACKGROUND: Left atrial compliance is an important determinant of symptoms in mitral stenosis. About one-third of patients with mitral stenosis have reduced left ventricular compliance. We measured the net atrioventricular compliance in rheumatic mitral stenosis patients noninvasively and analyzed if there were any clinical, electrocardiographic, roentgenographic or echocardiographic correlates of net atrioventricular compliance. METHODS AND RESULTS: Seventy-six patients with mitral stenosis were analyzed and as many normal subjects were taken as control group. Patients were divided into two groups--those 20 years and below were grouped as juvenile mitral stenosis and those above 20 years as adult mitral stenosis patients. The net atrioventricular compliance in patients with mitral stenosis was significantly impaired compared to normal population. Mean compliance in juvenile group was 4.66+/-2.18 ml/mmHg (range 2.17-9.6) and in adult group it was 4.79+/-1.99 ml/mmHg (range 2.04-8.9) (p = ns). There was no difference in net atrioventricular compliance between the juvenile and adult patients with mitral stenosis. Mitral valve area showed an independent positive correlation with net atrioventricular compliance. CONCLUSIONS: The net atrioventricular compliance was significantly reduced in patients with rheumatic mitral stenosis; however, there was essentially no difference in the net atrioventricular compliance between the juvenile and adult patients with mitral stenosis. The net atrioventricular compliance may not be responsible for the more severe symptoms observed in juvenile mitral stenosis.

Adolescent↗