IC50: 220 and 310 nM for human PLD1 and PLD2, respectively
Halopemide is a phospholipase D (PLD) inhibitor.
Phospholipase D (PLD) is a key enzyme for the production of phosphatidic acid, a lipid second messenger. Phosphatidic acid involves in both G protein-coupled receptor and receptor tyrosine kinase signal transduction networks.
In vitro: In a previous study, the IC50 of halopemide against PLD2 was found to be similar to that previously reported, but the compound had no preference for PLD2 over PLD1 [1].
In vivo: Animal study showed that the halopemide concentration in the rat brain was 10 times less than that of R29800, its chemical analog. However, the levels were the same in the pituitary gland. The highest level of halopemide was
Similarly as with different neuroleptics, the mechanism of action of haloperidol has not been totally clarified, but has been attributed to the inhibition of the transport mechanism of cerebral monoamines, particularly
Polyene target ergosterol which is main sterol component of fungal membranes. Eight AmB molecules bind eight ergosterol molecules through their hydrophobic moieties, with their hydrophilic sides forming a central channel of 70–100nm in diameter. Because of such channel, polyene leads to leakage of intracellular components such as K+ ions, hence cell lysis occur.
Sarpogrelate (MCI-9042) was shown to have the same affinity as ritanserin for 5-HT2A receptors, with a Ki value of 8.39 nM [1].
0.043), was dropped gradually from 12 h (FC=1.01) and markedly suppressed 24 h after the high-dose I+ treatments (FC= -1.48, p-value=0.006
Protein tyrosine phosphatases (PTPs) are reported to be involved in the etiology of diabetes mellitus, neural diseases such as Alzheimer and Parkinson diseases, regulation of allergy and inflammation, or PTPs are even regarded to be responsible for the pathogens.
ALDP is the protein that is responsible for the transport of the very long fatty acids to the peroxisome where breakdown of these very long fatty acids usually takes place. The gene known as the ABCD1 found in the X chromosome is mutated, leading to non-coding of the ALDP gene (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249072/ ).
Surfactant is a surface-active substance that is made of lipids and proteins that cover the alveoli and stabilize it and also protect the lungs by reducing the surface tension of pulmonary fluids (the amount of energy that is required to increase the surface of a liquid due to its molecular interaction bonds), that’s why alveoli don’t collapse when gas is exchanged in and out of the body (1). Phospholipids take up 80-85% of surfactant’s weight, and 40-50% is in form of disaturated (dipalmitoylphosphatidylcholine, DPPC). DPPC is in control for the surface tension decreasing the capability of surfactant. Surfactant is also composed of phosphtidylglycerol, phosphatiylethanolamine, sphingolmyelin, and cholesterol. Phospholipids in surfactant
The intracellular enzyme phospholipase C (PLC) hydrolyzes phospholipids specifically phosphatidylinositol-4,5-bisphosphate (PIP2) which is found in the inner layer of the plasma membrane.
Phenylthiocarbamide or PTC is a compound well known for it’s unique taste or in some cases lack of. Depending on the genetics of an individual, PTC can taste very bitter. Likewise however, if the individual is not a carrier for the gene than he/she will taste nothing. PTC’s unique ability was first discovered in 1931 by a chemist, Arthur Fox, and his partner, C. R. Noller. When PTC powder was dispersed in the air, Noller complained of a very bitter taste however Fox was unable to taste it. Initially curious, the duo tested other individuals and found that every person could be classified into two groups: tasters and non-tasters. (Wooding, 2006) Simply, If you are a homozygous dominant or a heterozygous than you are a carrier for the gene that
Phospholipids are compound lipids. They are also known as phosphatides. They are defined as esters of fatty acids with glycerol or any other alcohol and contain an esterified phosphoric acid and a nitrogenous base.
It was shown in section 3.5 that Azide – 2 significantly inhibited the growth of all three cell types: 4T1 – RLR, HT1080 – luc2 and HepG2 – luc2. Azide – 2 which was shown as the most potent competitor of glutamine uptake tested in this study also killed the cells with IC50 values at 0.1 – 0.2mM. As previously mentioned, only a very low concentration of Azide – 2 from 5 - 16µM was effective enough to reduce the glutamine uptake by these cell types to a half of maximal level. The mechanism by which the cell growth was disrupted quickly is still unclear. However, the extreme interference of glutamine uptake should be the first point to exploit the action of Azide – 2. Then, more experiments can be subsequently carried out to investigate the killing effect on the intracellular environment. In contrast to Azide – 2, Azide – 1 killed the cells slowly with the IC50 value at 0.55 – 3mM which is 5 – 30 fold higher than that of Azide – 2. The mode of Azide – 1’s toxicity to cells is quite consistent with the inhibition trend of glutamine uptake. As Azide – 1 bound and inhibited the glutamine uptake by 4T1 – RLR and HepG2 – luc2 cells better than HT1080 – luc2 cells, it affects the growth of the former two cell types more dramatically than the latter. Hence, the working mechanism on which the compound counted to
To put it simply, cholesterol is a waxy substance that is found in all cells of the body. The body needs cholesterol in order for the body to stay healthy. It is used to help the body make hormones, building blocks, and to digest food. Cholesterol is made by the body and is in some foods.
The cytoskeleton, network of polymeric structure is a highly dynamic framework comprised of microtubules polymerized from α- and β-tubulin subunits and microfilaments (AFs) polymerized from G-actin and related proteins. Numerous studies have shown the presence of cross-bridges between cortical microtubules and the PM, so they maintain a link and this linkage can extend to the cell wall (Akashi et al., 1990; Akashi and Shibaoka, 1991; Shibaoka, 1994; Sonobe and Takahashi, 1994). Plant cytoskeleton maintains proximity with the plasma membrane that provides an important platform for signal perception and transduction (Gilroy and Trewavas, 2001; Wasteneys and Galway, 2003). Above described proximity concept suggests this framework as a downstream targets of various signalling pathways. The bond arises between plasma membrane and cytoskeleton through a hydrophobic domain which present on the tubulin molecule or indirectly through interaction with an integral membrane protein (Sonesson et al., 1997). Phospholipase D (PLD) is a plasma membrane protein which has been characterized and confirmed for having the ability to make connection between cortical microtubules and the plasma membrane (Gardiner et al., 2001; Dhonukshe et al., 2003; Drobak et al., 2004; Hong et al., 2008). Therefore PLD has been suggested to function as a structural and signalling link between the plasma membrane and the cytoskeleton in Arabidopsis in tobacco (Gardiner et al., 2003). Cytoskeletal reorganization
Signaling lipids control multiple fundamental cellular processes, including endocytic trafficking and cell proliferation. However, our understanding of lipid-mediated cellular functions in Plasmodium parasites is still largely lacking. Among all the signaling lipids, phosphatidylinositol 3-phosphate (PI(3)P) has been recognized as crucial to parasite growth and survival. Emerging evidence has demonstrated that PI(3)P is localized to the membranes of two specialized organelles—the apicoplast and the food vacuole—in the blood-stage parasites where it facilitates apicoplast biogenesis and hemoglobin uptake. This distinct
The fastness of the immobilized lipase on the membrane is crucial to the long-term use of the EMBR latterly. The plot of the desorption ratio as a function of time is shown in Figure 7. The desorption ratio of the EMBR without using crosslinking agent reached 63.4% within 180 min, indicating a very week interaction between the membrane and purely physically adsorbed lipase. Therefore, the lipase can be easily flushed away under a high shear force condition. In contrast, the desorption ratio remained no more than 10% after crosslinking, owing to the resolution of the enzyme leakage problem during the operation.