2-Dipalmitoyl-Glycerol

Activators of GRK would cause phosphorylation of serine and threonine residues, which can then bind arrestin proteins, preventing reactivation of the signaling pathway.

The PI3Ks are linked to variety of different signaling pathways, but each version of the lipid enzyme has a similar PIK core region [2]. This region of the PI3K is composed of three essential parts: a C2 region, a helical region, and a catalytic region; it should be noted that in some forms of the PI3Ks these regions are split up on different subunits (refer to Figure 1 below) [2]. From these three structural components, the PI3K is able to carry out its important activating role and create the three products listed above. These products are noted to remain near the plasma membrane- on the cytosolic side- and to have their own biding sites [3]. The binding sites on the PI3K products are indications of the signaling pathway, and therefore attract other signaling proteins, like the serine-threonine kinases PKB and PDK1 [3]. It is also important to mention that the PI3K signal and its products can both be terminated by removing the phosphate added to the inositol ring of the phosphoinositide; this is done by the lipid phosphatase known as PTEN [3]. A termination step is important in the regulating activity of PI3Ks, and therefore in regulating the activities of the cell. From the medical field perspective, PI3Ks are important since they are linked to crucial pathways for insulin regulation and cell growth.

Regulation of DAG and phytoceramide by Ipc1. When Wild type and GAL7::IPC1 strains were exposed to galactose and glucose, DAG (activator of PKC1) levels in the GAL7::IPC1 strain increased when IPC1 was induced by galactose, and decreased when IPC1 was repressed by glucose. Furthermore, phytoceramide levels were increased when IPC1 was down regulated by glucose in the GAL7::IPC1 strain. In both wild type strains, no change was seen when IPC1 was up or down regulated, as expected (Fig. 2).

Another mechanism is the activated polyol pathway during hyperglycaemia consuming NADPH which is the essential cofactor for regenerating reduced glutathione. Depletion of glutathione lowers the threshold for intracellular oxidative damage.

Hexadecyl Methyl Glycerol is a structural analog of diacylglycerol with a hexadecyl chain at the sn-1 position and a methyl group at the sn-2 position. Hexadecyl Methyl Glycerol inhibited the activation of purified protein kinase C by diacylglycerol

glycerol remaining will be phosphorylated by glycerol kinase as ADP is produced from ATP to form glycerol 3-phosphate, making this reaction exothermic (ΔG’˚< 0). l-glycerol 3-phosphate is then oxidised by glycerol 3-phosphate

A practical problem that limits the use of tributyrin, which is a triacylglycerol composed of three butyric acid molecules esterified with glycerol, in in vitro experiments is the fact that tributyrin is highly unstable due to the Ostwald ripening effect, which is a process whereby larger droplets grow at the expense of smaller droplets due to molecular diffusion of oil molecules through the continuous aqueous phase separating the droplets. This may substantially affect results and cause great experiment-to-experiment variations. Based on this consideration, in the in vitro experiments we used sodium butyrate.

The Caenorhabditis elegans LET-23, which is an Epidermal Growth Factor (EGF) receptor, controls multiple developmental pathways. In humans, EGF receptor mutations are implicated in a large number of cancers due to excess signaling promoting cell growth and cell division. Recent work has shown that in C. elegans LET-23 may also affect lipid production, specifically that of the phospholipid phosphatidylcholine. To investigate the role of the LET-23 receptor on lipid production, I have examined the cellular location of a fluorescent-tagged SBP-1 marker under different conditions within the worm and from these inferred levels of lipid production. I will discuss my results and their impact on our understanding of EGF signaling and lipid biosynthesis.

In diabetic neuronal cells, hyperglycemic flux activates four cellular pathways: the polyol, advanced glycation end-product, protein kinase C, and hexosamine pathways increasing

Kinase gain of function (GOF) analysis: The hit cDNAs of kinases will be co expressed along with cDNAs Htt exon 1, Htt 171 and Htt 586 containing 16Q-23Q in HEK 293 cells and the Phosho S13/s16 and S116 Htt will be examined using the appropriate antibody, Phos –tag SDS-PAGE method (Bustamante et al., 2015) also method of IP of Htt and mass spectrometry. Kinases will also be co expressed with appropriate S to A variants of the above Htt cDNAs to confirm the specificity of phosphorylation and definitive site of phosphorylation. We will also test any pharmacological or genetic method to activate kinases of interest (ex. Phosphatase inhibitors or siRNA that can increase the

Peptidoglycan deacetylases, is a member of polysachcharide deacetylase family (pfam01522) of enzyme, which share the conserved polysaccharide domain also know as “NodB homology domain” with chitin deacetylases, acetylxylan esterases, xylanases, rhizobial NodB chitooligosaccharide deacetylases (1,2). Peptidoglycan N-acetylglucosamine deacetylase (PgdA) (EC 3.5.1.-), catalyzes the removal of the acetyl group from the C2 atom of N-acetylglucosamine, a constituent of the peptidoglycan found in the cell walls of many bacteria. This modification of peptidoglycan is very important as the intracellular immune receptor nucleotide-binding oligomerization domain (NOD1 and NOD2) proteins of human cells no longer recognize the modified peptidoglycan and not able to initiate innate immune response by inducing autophagy or by activating the NF-kB pathway against the pathogens (3,4,5,6). Modified peptidoglycan also become resistant to lysozyme action and contributed to survival in the host (7,15, 17). PgdAs are identified as virulence factor and pathogenic bacteria use it to deacetylate of their own peptidoglycan as a mechanism to escape the recognition by the host (8,9). As a result PgdAs is becoming a target for the design of new drugs to aid the host recognition and block the immune leakage.

Obesity is known to produce a number of stress and inflammation responses in the body that lead to the activation of the inflammatory signalling molecules, Jun NH2-terminal kinase (JNK) and inhibitory kB kinase (IKK). Activation of these pathways plays a key part in the development of insulin resistance followed by progression to diabetes as they greatly affect inflammatory responses, insulin signalling, and lipid and glucose homeostatis (Nakamura et al. 2014). For example, activating the JNK pathway leads to serine phosphorylation of insulin receptor substrate (IRS) proteins which results in inhibited insulin signalling and thus insulin resistance. Double-stranded RNA-dependent protein kinase (PKR) has recently been shown to control the JNK and other major inflammatory pathways, to directly inhibit insulin signalling, to be activated by fatty acids as well as endoplasmic reticulum (ER) stress, and to be necessary for the activity of inflammasomes (Nakamura et al. 2010; Komiya et al. 2010; Lu et al. 2012). Moreover, PKR has been found to be highly activated in obese people as well as mice with genetically and diet-induced obesity, especially in adipose and hepatic tissues (Boden et al. 2008; Nakamura et al. 2010; Carvalho-Filho et al. 2012). Finally, recent studies have found that PKR knockout obese mice were protected against both IR and obesity-triggered inflammation and that administration of PKR inhibitors reduced JNK activation, reduced inflammation in adipose

Raucci A, Cugusi S, Antonelli A et al . A soluble form of the receptor for advanced glycation end products (RAGE) is produced by proteolytic cleavage of the membrane-bound form by the sheddase a disintegrin and metalloprotease 10 (ADAM10). FASEB J. 2008;22(10):3716-27.

Phospholipases are ubiquitous enzymes that hydrolyses phospholipids mainly glycerophospholipids and also neutral lipids into various signaling products which includes phosphatidic acid (PA), diacylglycerol (DAG), free fatty acids (FFAs), and lysophospholipids (LPLs) that are involved in regulating numerous processes such as cytoskeletal dynamics, homeostasis, membrane remodeling, microbial virulence, nutrient acquisition, secretion and signal transduction (Kohler et al., 2006; Hong et al.,

TPI is a dimeric glycolytic enzyme, which catalyzes the isomerization of D-glyceraldehyde-3-phosphate to dihydroxyacetone phosphate. TPI is a crucial and highly conserved component of glycolysis pathway. Following DC activation, glucose has to be processed by glycolysis pathway to generate pyruvate and ATP. Pyruvate can be converted to Lactic acid which is secreted into extracellular space. This pathway allows immune cells such as DCs to produce ATP at a higher rate than oxidative phosphorylation. Inconsistent with our findings that F2HIC-matured DCs express lower amount of TPI, it has been shown that TLR agonists stimulate a profound metabolic transition to aerobic glycolysis, similar to the Warburg effect displayed by cancer cells (Krawczyk et al. , 2010). Actually, we found lower TPI expression (indicator of glycolysis) in F2HIC-matured DCs compared to LPS-matured DCs suggesting lower potency for