The sphingolipids are primarily situated in the noncytoplasmic leaflet of cellular membranes contribute to the structural integrity and fluidity characteristics of cell membranes and signal transduction complexes. Ceramide sits at the hub of sphingolipid metabolism as the neutral, lipid building block for complex sphingolipids and glycosphingolipids, serving as a substrate for more than 11 different enzymes Ceramide is also a key intermediate for the biosynthesis of the major plasma membrane sphingolipids like  Sphingomyelin(SM) and Glycosphingolipids (GSLs). Ceramides typically induces growth arrest and apoptosis, whereas S1P promotes cell proliferation and survival. Other sphingolipids such as sphingosine and sphinganine also function as pro-apoptotic factors.[..]

Sphingosine-1-phosphate (S1P) is a bioactive sphingomyelin derivative that is present in plasma and serum at high nanomolar concentrations. S1P acts via the specific cell surface G-protein-coupled receptors, S1P1-5. S1P1 and S1P2 were originally identified from vascular endothelial cells (ECs) and smooth muscle cells, respectively. S1P receptors modulate multiple intracellular pathways and thereby regulate central cellular processes, such as survival, proliferation and cytoskeletal organization. S1P, which directly acts on ECs, is involved in the regulation of angiogenesis and mural cell recruitment during development and in the adult.  Vascular endothelial cell growth factors (VEGFs), on the othe hand, are recognized as the most crucial driver of vasculogenesis[..]

The experience of pain in response to noxious stimuli serves a crucial biological purpose: it alerts a living organism to environmental dangers, inducing behavioral responses that protect the organism from further damage. In contrast, chronic pain arising from disease states and/or pathological functioning of the nervous system offers no advantage and may be debilitating to those afflicted. Control and treatment of chronic pain remain major clinical challenges. The calcium-sensing protein DREAM (Downstream Regulatory Element Antagonistic Modulator) is a putative transcriptional repressor involved in modulating pain (Ref.1).DREAM is constitutively expressed in certain neurons and transcriptional activity of the repressor DREAM depends on its high affinity binding to a[..]

Helicobacter pylori is a gram negative bacterium that causes chronic inflammation in essentially all hosts, a process that increases the risk of developing peptic ulceration, distal gastric adenocarcinoma, and gastric mucosal lymphoproliferative disease. This bacterium also is the most common cause of ulcers worldwide. H. pylori infection is most likely acquired by ingesting contaminated food and water and through person to person contact. The infection is more common in crowded living conditions with poor sanitation. Infected individuals usually carry the infection indefinitely unless they are treated with medications to eradicate the bacterium. One out of every six patients with H. pylori infection develops ulcers of the duodenum or stomach. H. pylori are also[..]

The macrophage differentiation system in mouse establishes the fact that, the macrophages stop proliferate during the process of cell differentiation. Induction of METS (Mitogenic Ets Transcriptional Suppressor METS) otherwise known as Ets (E26 Avian Leukemia Oncogene) repressor, leads to terminal differentiation and cell cycle arrest. Inside macrophages, METS blocks HRas1 (Harvey Rat Sarcoma Virus Oncogene-1)-dependent proliferation without inhibiting HRas1-dependent expression of cell type-specific genes by selectively replacing Ets activators on the promoters of cell cycle control genes. Anti-proliferative effects of METS require its interaction with Ddx20 (DEAD (Asp-Glu-Ala-Asp) Box Polypeptide-20) that assembles a novel co-repressor complex (Ref.1 and 2). The[..]

Estrogens are a class of steroid hormones that play a central role in reproduction, and are regarded as the powerful female hormones that make a girl develop into a woman capable of reproduction. Estrogenic steroids, that include: E1 (Estrone), E2 (Estradiol/17-beta Estradiol) and E3 (Estriol), regulate cellular functions in a wide variety of tissues and influence proliferation in the female reproductive tract and mammary gland. It is this proliferative role of these hormones that, a woman's risk for breast and uterine cancer is often associated with lifetime exposure to estrogen. Estrogens induce proliferation of cancer cells by stimulating G1/S transition and the subsequent progression of cell cycle (Ref.1).In the uterus, estrogen triggers the proliferation of[..]

Biological membranes are composed of hundreds of distinct proteins and phospholipids. Phospholipids are diacylglycerol derivatives with a hydrophilic, zwitter ionic, often charged headgroup at position  C3  of the glycerol backbone. The properties of phospholipids give lipid bilayer membranes their self-organizing structure. Phospholipids are usually composed of two fatty acid chains esterified to two of the carbons of glycerol phosphate, the phosphate being esterified to a hydroxyl group of another hydrophilic compound, such as choline, ethanolamine or serine.In general, E. coli and most related gram-negative bacteria do not contain phosphatidylcholine, phosphatidylinositol, sphingolipids, glycolipids, plasmalogens, or sterols, which are characteristic of[..]

RNAi (RNA interference) is broadly defined as a gene silencing pathway that is triggered by dsRNA (double-stranded RNA). The dsRNA trigger can be supplied exogenously, as an experimental tool, or can derive from the genome. RNAi involves a number of steps from biogenesis of the trigger RNA, processing of dsRNA to small RNAs and formation of an effector complex containing the small RNA which goes on to guide mRNA cleavage, translational repression and/or chromatin modifications in a sequence-specific manner. Two types of small RNA molecules – miRNA (microRNA) and siRNA (small interfering RNA) – are central to RNA interference (Ref. 1, 2 and 9). siRNAs and miRNAs are 20–25-nt RNAs involved in silencing homologous genes or their transcripts. miRNAs[..]

Myocardial hypertrophy is an adaptational response of the heart to increased work load, but it is also associated with a high risk of cardiac mortality due to its established role in the development of cardiac failure, one of the leading causes of death in developed countries (Ref.1). The hypertrophic growth of the myocardium is initiated by a wide array of endocrine, paracrine, and autocrine growth factors in response to biomechanical stress, increased workload, injury, or, intrinsic defects in contractile performance. Cardiac hypertrophy eventually normalizes the increase in wall tension, thereby abrogating the initial stimulus. Although initially beneficial, sustained cardiac hypertrophy can lead to decompensation and cardiomyopathy, the leading predictors of heart[..]

All organisms are exposed to a multitude of DNA damaging agents ranging from UV (Ultraviolet) light to fungal metabolites, like Aflatoxin B1. Furthermore, DNA damaging agents, such as ROS (Reactive Oxygen Species), can be produced by cells themselves as metabolic byproducts and intermediates. Together, these agents pose a constant threat to an organism's genome. As a result, organisms have evolved a number of vitally important mechanisms to repair DNA damage in a high fidelity manner. They have also evolved systems (cell cycle checkpoints) that delay the resumption of the cell cycle after DNA damage to allow more time for these accurate processes to occur. If a cell cannot repair DNA damage accurately, a mutagenic event may occur (Ref.1). Most bacteria,[..]

Telomeres are specialized nucleoprotein structures found at the ends of linear eukaryotic chromosomes. Telomeres confer stability to chromosomes by preventing nucleolytic degradation and recombination. They also function in chromosomal localization, nuclear architecture, and repression of nearby genes. The telomeric DNA of most organisms consists of simple tandem repeats that are rich in dG and dT residues on the 3' end-containing strand. This strand is synthesized by a ribonucleoprotein complex called telomerase, an enzyme that is critical to the maintenance of telomere length and function (Ref.1).The telomeres of the budding yeast Saccharomyces cerevisiae contain ~300 base pairs of double-stranded (TG1-3/C1-3A) sequences. Telomerase recruitment is mediated by a[..]

AIF (apoptosis-inducing factor), is a phylogenetically old flavoprotein which is confined to the mitochondrial intermembrane space in healthy cells but upon lethal signaling, it translocates, via the cytosol, to the nucleus where it binds to DNA and provokes Caspase-independent chromatin condensation [Ref.1]. Proteolysis of the membrane tether in mature AIF can be mediated by local or cytoplasmic proteases entering the intermembrane space upon permeabilization of the outer membrane. Mitochondrial membrane permeabilization leads to the release of other IMS (Intermembrane Space) proteins, such as CYCS (Cytochrome-C), SMAC (Second Mitochondria-Derived Activator of Caspase12)/DIABLO and ENDOG that take part in the apoptotic process. BCL2L1 (Bcl2 Related Protein Long[..]