Smooth endoplasmic reticulum? | Yahoo Answers
Thus the main function of the rough endoplasmic reticulum and the outer nuclear membrane is to serve as a port of entry of secretory, lysosomal, and integral. Structure of rough endoplasmic reticulum yahoo dating Rough endoplasmic reticulum is a cell organelle whose main function is synthesis of. Looking for online definition of Endoplasmic reticulum, smooth in the Medical The structure functions in the synthesis of proteins and lipids and in the transport .
Reduced blood flow resulting from arterial occlusion or cardiac arrest is closely associated with tissue hypoxia and hypoglycemia that cause protein misfolding and ER stress Elevated triglycerides and hypercholesterolemia induces ER stress in vascular cells. Similarly, addition of macrophages with cholesterol was shown to induce ER stress, enhancing expression of cytokines in presence of CHOP induction, which further implicates the UPR in the atherosclerosis mechanism.
Abnormal deposition of free cholesterol in coronary arteries is toxic to many different vascular cell types, including macrophages, endothelial cells and smooth muscle cells. This condition leads to apoptosis of vascular cells, which is believed to promote atherosclerosis Under regular homeostatic conditions, the majority of normal cells do not experience ER stress.
The expression of GRP78 and other glucose-regulated proteins are induced during tumour growth. During tumourigenesis, the high proliferation index of cancer cells requires increased activities of ER protein folding, assembly and transport, a condition that can induce physiological ER stress Following initiation of malignancy, poor vascularisation in tumours results in hypoxia, hypoglycemia and acidosis. All these processes are strong inducers of UPR pathways.
In addition, some cancer cells express mutant proteins that cannot be correctly folded and activate UPR. Unlike normal cells, most cancer cells express chronically elevated baseline ER stress levels, as indicated by permanently increased expression of GRP78 However, during conditions of prolonged stress, GRP78 remains bound to misfolded proteins in the lumen of the ER in order to repair them, and therefore permanently dissociated from the UPR proteins that continue to stimulate expression of CHOP.
As a consequence, CHOP expression remains increased under these conditions, thus leading to apoptosis Elevated Grp78 level has been reported to correlate well with higher pathologic grade, recurrence rate and poor prognosis in patients with breast, liver, prostate, colon and gastric cancers and suppression of GRP78 inhibited the proliferation of cancer cells Chemical or pharmaceutical chaperones are a group of low-molecular weight compounds that have been proposed to increase ER folding capacity by facilitating proper folding and decreasing the accumulation and aggregation of misfolded proteins in the ER lumen 37 For example, in mouse models, 4-phenyl butyrate 4-PBA and taurine-conjugated deoxycholic acid TUDCA have been shown to provide benefit for numerous ER stress-related diseases including T2D, atherosclerosis and leptin resistance.
However, their precise ER stress-relieving properties remain unknown. Increases the expression of ER chaperones such as Grp78 and Grp94 and has beneficial effects in in vitro models of neurodegenerative diseases However, it is difficult to develop therapeutic approaches specifically targeting ER stress because UPR signaling exerts dual biological functions related to both survival and apoptosis.
Therapeutic induction of ER stress-induced apoptosis may be beneficial in killing cancer cells. As an example, inhibition of proteasome activity, which degrades misfolded proteins, induces ER stress in cancer cells.
For example, bortezomib which is a selective proteasome inhibitor used for killing multiple myeloma cells and provides antitumour activity in the treatment of pancreatic cancer ER stress, considered as both a cause and consequence of metabolic disturbances, results in UPR activation.
Under ER stress, cells recognise perturbations of ER homeostasis and direct the UPR signal to either survival or apoptosis pathways, depending on the intensity of ER stress. In contrast, dysfunction of the UPR pathway or chronic ER stress, may contribute to the pathogenesis of numerous human diseases. Therefore, in future an understanding of the cause of protein misfolding, aggregation and genetic environmental susceptibility induced ER stress.
In addition, new therapeutic agents must be carefully tested in appropriate mouse models to avoid possible adverse effects of ER stress-associated diseases. Molecular biology of the cell. Ozcan L, Tabas I. Role of endoplasmic reticulum stress in metabolic disease and other disorders.
Endoplasmic reticulum stress and type 2 diabetes. Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. Targeting endoplasmic reticulum stress for cancer therapy.
Front Biosci Schol Ed. Cell death and endoplasmic reticulum stress: Nat Rev Drug Discov. Structure and intermolecular interactions of the luminal dimerization domain of human IRE1alpha. On the mechanism of sensing unfolded protein in the endoplasmic reticulum. Enhanced integrated stress response promotes myelinating oligodendrocyte survival in response to interferon-gamma. Tabas I, Ron D. Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress.
Hummasti S, Hotamisligil G.
Endoplasmic reticulum stress and inflammation in obesity and diabetes. Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-I.
Bortezomib sensitizes pancreatic cancer cells to endoplasmic reticulum stress-mediated apoptosis. The unfolded protein response at the crossroads of cellular life and death during endoplasmic reticulum stress.
What is the function of smooth endoplasmic reticulum? | Yahoo Answers
Targeting the endoplasmic reticulum-stress response as an anticancer strategy. The unfolded protein response. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease.
Perk promotes cancer cell proliferation and tumor growth by limiting oxidative DNA damage. Inositol-requiring enzyme 1alpha is a key regulator of angiogenesis and invasion in malignant glioma. Over expression of human x-box binding protein 1 XBP-1 in colorectal adenomas and adenocarcinomas.
Genetic predisposition for type 1 diabetes mellitus — the role of endoplasmic reticulum stress in human disease etiopathogenesis. Endoplasmic reticulum stress is reduced in tissues of obese subjects after weight loss. Coping with endoplasmic reticulum stress in the cardiovascular system. Madonna R, de Caterina R.
Prolonged endoplasmic reticulum stress in hypertrophic and failing heart after aortic constriction: Ischemic preconditioning protects cardiomyocytes against ischemic injury by inducing GRP Biochem Biophys Res Commun.
ER stress and diseases. An involvement of oxidative stress in endoplasmic reticulum stress and its associated diseases. Int J Mol Sci.
Bioline International Official Site (site up-dated regularly)
Boyce M, Yuan J. Cellular response to endoplasmic reticulum stress: Luo B, Lee AS. The critical roles of endoplasmic reticulum chaperones and unfolded protein response in tumorigenesis and anticancer therapies. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Endoplasmic reticulum stress plays a central role in development of leptin resistance.
Smooth endoplasmic reticulum?
Regulation of ER stress proteins by valproate: A molecular chaperone inducer protects neurons from ER stress. Selective inhibition of eukaryotic translation initiation factor 2 alpha dephosphorylation potentiates fatty acid-induced endoplasmic reticulum stress and causes pancreatic beta-cell dysfunction and apoptosis.
Refbacks There are currently no refbacks. Copyright c Journal of Pharmaceutical and Biomedical Sciences. Cerebrosides are monoglycosylceramides in which glucose or galactose sugar residue is attached by O-ester linkage to the primary alcohol of the ceramide. Glycosphingolipids containing more than one sugar moiety belongs to the oligoglycosylceramide group. They are vital components of cellular membranes of most eukaryotic organisms and some bacteria [ 2 ].
They are divided into two groups: These are glycosphingolipids carrying a sulfate ester group attached to the carbohydrate moiety. Sulfated is mainly formed of 3-sulfate esters of galactosylcerebrosides galactosylsulfate esters.
They are mainly found in tissues that are very active in sodium transport such as kidneys, salt glands and gills [ 3 ]. This group of glycosphingolipids consists of molecules composed of ceramide linked by a glycosidic bond to an oligosaccharide chain containing hexose and sialic acid units.
One of the common monosialo-gangliosides is ganglioside GM1. Distribution of Glycolipids in the Cell Most of the glycolipids are distributed in membranous structures in the cell. Two-thirds of the total glycolipids are distributed in intracellular membranes such as golgi apparatus, endosomes, lysosomes, nuclear membrane, endoplasmic reticulum, and mitochondria [ 4 ]. Glycolipids are synthesized in golgi apparatus by the addition of saccharides one by one to the ceramide moiety.
Most glycolipids are transported between membranes as small vesicles maintaining a bilayer structure. However, the first step of the biosynthesis of most glycosphingolipids i. Some glycolipids are also distributed in cytosol.
Glycolipids are distributed prudentially into exofacial leaflets of plasma membrane and the luminal side of organelles [ 6 ]. In polarized epithelial cells, glycosphingolipid are enriched on apical side of the cells while cells with polarity, e.
Simons and Toomre [ 7 ] observed that in plasma membrane, glycosphingolipids along with cholesterol form clusters, called rafts. This region had relatively less phospholipids than other areas of plasma membrane. Rafts are lateral assemblies of sphingolipids and cholesterol that form tight hydrophobic interactions between these molecules.
Brown and London [ 8 ] reported that sphingolipids associate laterally with one another through weak interactions between the carbohydrates heads of the glycosphingolipids and the hydrophobic interactions between their saturated side chains and any void between associated glycosphingolipids were filled by cholesterol molecules which interact with hydrophobic portions of glycolipids. The tight interactions between cholesterol and glycolipids in the membrane are the driving force that segregates them from phospholipids that remain fluid in nature [ 9 ].
Carbohydrate-Carbohydrate Interaction of Glycolipids Cell-cell interactions play an important role in the development, maintenance, and host-pathogen interaction. They are highly dynamic processes, which include migration, recognition, signaling, adhesion, and finally attachment. Carbohydrates moieties of glycolipids, the most prominently exposed structures on the surface of living cells, with flexible chains and many potential binding sites are ideal to serve as important players in these events.
Molecular interactions where carbohydrates are involved are usually considered as weak interactions, and therefore, there is biological relevance of carbohydrate-carbohydrate and carbohydrate-protein interactions [ 10 ]. Glycolipid-glycolipid interaction is a rapid process, as compared with protein-protein interaction, although the strength of the interaction is weaker than that of protein-protein interaction [ 10 ].
A synergistic effect between cell adhesion based on glycosphingolipidsglycosphingolipids interactions and adhesion based on integrins was observed by Bucior et al. They postulated that glycosphingolipidglycosphingolipid interaction may define the initial specificity and direction of the cell recognition and regulate the adhesion process.
One of the important properties of the bilayer is the ability to orient and cluster glycolipid species in such a way so that interactions in the biological systems are maximized. The lipid moiety of glycolipids is generally buried in the cell membrane bilayer, leaving the oligosaccharide moieties exposed but in close proximity to the bilayer surface [ 12 ].
This represents a unique environment for carbohydrate interactions with other molecules.
Glycolipids cause two types of interactions. They interact side by side within the same membrane to form clusters and by trans interactions in which two interfacing membrane interact through their surface carbohydrates [ 13 ]. They further reported that trans interactions between the glycolipids provides the basis for glycosphingolipids-dependent cell to cell adhesion, which takes place through specific complementary structures catalyzed in many cases by calcium ions.
Therefore, cell surface complex carbohydrate has emerged as key recognition molecules, mediating physiological interactions between cells. Typically glycans on one cell surface engaged by complementary carbohydrate binding proteins on opposing cells, initiate a cellular responses [ 14 ]. The preliminary evidence for carbohydrate-carbohydrate interaction came from the studies of liposomes containing highly purified glycosphingolipids.
Glycosphingolipids bind to the complementary glycosphingolipids through interaction between their carbohydrate moieties [ 15 ]. Cell surface carbohydrates play a major role in cell-cell or cellsubstrate recognition. The interaction between these two lipids could be either a lateral cis interaction in the same bilayer or a trans interaction between apposed bilayers and may be involved in stabilization of the myelin sheath.
Schnaar [ 17 ] observed that human leukocytes were recognized by E-selectins present on vascular endothelium during inflammation.
The recruitment of neutrophils to sites of inflammation was mediated by endothelial leukocytes adhesion molecule-1 ELAM-1 expressed on activated endothelial cells of blood vessels walls. ELAM-1 is a member of the selectin family of adhesion molecules that contain a lectin motif thought to recognize carbohydrate ligands. The sialyl Lewis A and sialyl Lewis X, the carbohydrate determinants which are frequently expressed on human cancer cells, serve as ligands for a cell adhesion molecule of the selectin family, E-selectin, which is expressed on vascular endothelial cells.
These carbohydrate determinants are involved in the adhesion of cancer cells to vascular endothelium and thus contribute to hematogenous metastasis of cancer by triggering the activation of integrin molecules through the action of several cytokines leading to extravasation of cancer cells. Overall, it can be stated that carbohydrate-carbohydrate interactions play an important role in recognition and signaling events in a variety of biological phenomena.
Biological Functions of Membrane Glycolipids Membrane glycolipids perform a number of functions in biological system. Glycolipids have roles in response to cell contact, as receptor components, as anchors for proteins and as markers for tumor progression and cell differentiation [ 18 ].
Glycolipids as signal transducers Glycolipids have been known to be modulators of signal transduction. Glycosphingolipids and sphingomyelin in animal cells are clustered and organized as membrane microdomains closely associated with various signal transducer molecules such as cSrc, Src family kinases, small G-proteins e.
RhoA, Rasand focal adhesion kinase. Glycosphingolipid clustering in such microdomain causes adhesion to complementary glycosphingolipids on the surface of counterpart cells through carbohydrate-carbohydrate interaction. Glycosphingolipids dependent cell adhesion in microdomain causes activation of the signal transducers, leading to cell phenotypic changes [ 1920 ] Glycosphingolipid microdomains mediate signal response either by associating with GPI-anchored proteins or Immuno and growth factor receptors.
GPI-anchored proteins having saturated acyl chains were likely to insert preferentially into glycosphingolipid microdomains. They observed that antibody or ligand -mediated crosslinking of GPI-anchored proteins induces activation of src-family kinases and transient increase in tyrosine phosphorylation of several substrates. Reports showed that enzymatic removal of the carbohydrate moiety from cell-surface glycosphingolipids impairs the activation of the src-family kinase by antibody-mediated crosslinking of GPI-anchored protein.
Glycosphingolipid microdomains are also involved in signaling by immunoreceptors and growth factor receptors [ 21 ].