Current Medicinal Chemistry - Volume 19, Issue 24, 2012

Chromogranin A (CgA), a major component of the chromaffin granules, is co-stored and co-released with catecholamines. It is also expressed in extra-adrenal sites, including the heart. In the rat, CgA localizes in atrial myoendocrine cells, associated with Atrial Natriuretic Peptide (ANP), and in the conduction system. In the human heart it is present in the ventricular myocardium, co-localized with B-type NP (BNP). CgA is the pre Read More

Chromogranin A (CgA) is an acidic glycoprotein belonging to a family of regulated secretory proteins stored in the dense core granules of many neuroendocrine cells and neurons. This protein is produced, in certain conditions also by cardiomyocytes, keratinocytes and granulocytes. Upon secretion CgA is released in the extracellular environment and then in circulation. Increased levels of circulating CgA have been detecte Read More

The involvement of Chromogranin A (CgA) in the cardiovascular function regulation is attributed to its function as a prohormone. Several studies indicated that CgA-derived peptides, particularly Vasostatin-1 (VS-1) and Catestatin (CST), exert signaling effects in numerous organs/systems, including the cardiovascular system. This review focuses on the recently described signaling pathways activated by VS-1 and CST, giving Read More

Cardiomyocytes contain secretory granules in which chromogranins and several types of natriuretic peptides and growth factors are stored in addition to high Ca2+ concentrations. Yet the expression and serum levels of chromogranins and natriuretic peptides have been closely correlated with pathological cardiac hypertrophy and heart failure. Moreover, in distinction from the physiological cardiac hypertrophy that appear Read More

Chromogranin A (CgA) is produced by cells of the sympathoadrenal system and by human ventricular myocardium. In the clinical setting CgA has been mainly used as a marker of neuroendocrine tumors, but in the last decade a plenty of data have been published on the role of CgA and its derived peptides, particularly catestatin and vasostatin, in the regulation of cardiovascular function and diseases, including heart failure Read More

Serpinins are a family of peptides derived from proteolytic cleavage of the penultimate and the last pair of basic residues at the C-terminus of Chromogranin A. Three forms of naturally occurring serpinin have been found in AtT-20 pituitary cells and rat heart. They are serpinin, pyrogutaminated (pGlu) -serpinin and a C-terminally extended form, serpinin-RRG. In addition pGlu-serpinin has been found in brain, pri Read More

To date, many scientific attempts have been directed towards the development of experimental models for the identification of neuronal mechanisms evoking cardiovascular and hemodynamic dysfunctions. The spontaneously hypertensive rat (SHR), a genetic model of essential hypertension, has become a valuable rodent for the characterization of molecular markers in hypertensive-related diseases. Recently, g Read More

New endogenous antimicrobial peptides (AMPs) derived from chromogranin A (CgA) are secreted by nervous, endocrine and immune cells during stress. They display antimicrobial activities by lytic effects at micromolar range using a pore-forming mechanism against Gram-positive bacteria, filamentous fungi and yeasts. These AMPs can also penetrate quickly into neutrophils (without lytic effects), where, similarly to “cell pen Read More

Cerebral small-vessel disease (SVD) is a well-known cause of stroke, dementia and death, but its pathogenesis is not yet completely understood. The spectrum of neuroradiological manifestations associated with SVD is wide and may result from chronic and diffuse or acute and focal ischemia (leukoaraiosis and lacunar infarction) as well as from small-vessel rupture (cerebral microbleeds and intracerebral hemorrhage). Severa Read More

— 2-Methoxyestradiol (2ME2), a natural metabolite of estradiol which has no estrogenic activity, is a potent antitumor and anti-angiogenic compound, currently undergoing clinical trials for treatment of a variety of cancers. In the last two decades, an ever increasing number of synthetic 2-methoxyestradiol analogues have been reported. Structural changes include A/B/C/D-rings modification, homologation, aromatization, Read More

Protein aggregation and amyloid fibrillation can lead to several serious human diseases and protein drug ineffectiveness. The complexity and dynamics of protein folding present unique challenges for elucidating the molecular mechanisms involved in protein aggregation and designing effective amyloid inhibitors. Continuous development of creative approaches to identify an ultimate solution for controlling protein aggre Read More

Resveratrol (3,5,4'-trans-trihydroxystilbene) is a naturally occurring phytoalexin that is found in medicinal plants, grape skin, peanuts and red wine. Resveratrol exhibits a remarkable range of biological activities, including anticancer activity, antitubulin activity, anti-cardiovascular disease activity, etc. Several other natural products are structurally similar to resveratrol and also present in food. In addition, a series of resveratrol deri Read More

Antimicrobial resistance is an ever-increasing problem throughout the world and has already reached severe proportions. Bacteria can develop ways to render traditional antibiotics ineffective, raising a crucial need to find new antimicrobials with novel mode of action. We demonstrate here a novel class of pyrazine functionalized Ag(I) and Au(I)-NHC complexes as antibacterial agents against human pathogens that are resistant Read More

Preclinical pharmacological characterization of a novel inhibitor (UM8190) of prolylcarboxypeptidase (PRCP) was investigated. We synthesized and evaluated a library of proline-based analogs as prospective recombinant PRCP (rPRCP) inhibitors and inhibitors of PRCP-dependent prekallikrein (PK) activation on human pulmonary artery endothelial cells (HPAEC). Among the newly synthesized compounds, UM8190 was further charac Read More