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Cellular compartment

About: Cellular compartment is a research topic. Over the lifetime, 1082 publications have been published within this topic receiving 53794 citations. The topic is also known as: cell compartmentation.


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Journal ArticleDOI
TL;DR: It is concluded that microsomal steroid sulphatase and lysosomal enzymes share several cellular compartments.
Abstract: Immunocytochemistry was used to study the subcellular localization of steroid sulphatase in cultured human fibroblasts. Ultra-thin cryosections were incubated with antibodies raised against steroid sulphatase purified from human placenta and immune complexes were visualized with gold probes as electron dense markers. Steroid sulphatase was found in rough endoplasmic reticulum, Golgi cisternae and in the trans-Golgi reticulum, where it co-distributes with lysosomal enzymes and the mannose 6-phosphate receptor. The enzyme was not detected in lysosomes. Steroid sulphatase was also found at the plasma membrane and in the endocytic pathway (i.e. coated pits, endosomes and multivesicular endosomes). These may be the sites where sulphated oestrogen precursors are hydrolysed. Also here, it co-localizes with lysosomal enzymes and the mannose 6-phosphate receptor. It is concluded that microsomal steroid sulphatase and lysosomal enzymes share several cellular compartments.

41 citations

Journal ArticleDOI
TL;DR: The expression of IκB‐β in the differentiated surface epithelium of the colon may help these cells act as an immunological barrier to prevent activation of the mucosal immune system.
Abstract: The intestinal epithelium is spatially segregated into two compartments, one containing undifferentiated cells in a proliferative state and one with non-proliferative differentiated cells. Al- though this epithelium can produce many immune- modulating substances, emerging evidence suggests that the differentiated cell compartment is less immune responsive. Indeed, it is the differentiated cellular compartment that represents the interface between the highly antigenic luminal environment and the mucosal immune system. The NF-kB/rel family of transcriptional activators play a critical role in regulating the inflammatory response by activating a wide variety of immune-modulating genes. These transcription factors are maintained in an inactive state in the cytoplasmic compartment by interaction with inhibitory proteins of the IkB family. In this study we show by immunohistochem- istry that IkB-b is expressed at high levels specifi- cally in the differentiated surface epithelium of the colonic mucosa. Using a naturally occurring com- pound found in the colon of vertebrates, butyrate, we provide evidence in an intestinal cell line that alteration of IkB-b expression can modulate the transcriptional activation of the interleukin-8 (IL-8) gene by preventing the nuclear translocation of NF-kB proteins. Therefore, the expression of IkB-b in the differentiated surface epithelium of the colon may help these cells act as an immunological barrier to prevent activation of the mucosal im- mune system. J. Leukoc. Biol. 66: 1049-1056; 1999.

41 citations

Journal ArticleDOI
TL;DR: In this article, the authors describe the transport of phospholipids between mitochondria and other organelles, and discuss recent developments in understanding of the molecular functions of the protein complexes that mediate these processes.

41 citations

Journal ArticleDOI
TL;DR: Data demonstrate the utility of SCH to predict quantitatively total tissue accumulation and elucidate mechanisms of hepatocellular drug accumulation such as active uptake versus binding/sequestration.
Abstract: Prediction of clinical efficacy, toxicity, and drug-drug interactions may be improved by accounting for the intracellular unbound drug concentration (Cunbound) in vitro and in vivo. Furthermore, subcellular drug distribution may aid in predicting efficacy, toxicity, and risk assessment. The present study was designed to quantify the intracellular Cunbound and subcellular localization of drugs in rat sandwich-cultured hepatocytes (SCH) compared with rat isolated perfused liver (IPL) tissue. Probe drugs with distinct mechanisms of hepatocellular uptake and accumulation were selected for investigation. Following drug treatment, SCH and IPL tissues were homogenized and fractionated by differential centrifugation to enrich for subcellular compartments. Binding in crude lysate and cytosol was determined by equilibrium dialysis; the Cunbound and intracellular-to-extracellular Cunbound ratio (Kpu,u) were used to describe accumulation of unbound drug. Total accumulation (Kpobserved) in whole tissue was well predicted by the SCH model (within 2- to 3-fold) for the selected drugs. Ritonavir (Kpu,u ∼1) was evenly distributed among cellular compartments, but highly bound, which explained the observed accumulation within liver tissue. Rosuvastatin was recovered primarily in the cytosolic fraction, but did not exhibit extensive binding, resulting in a Kpu,u >1 in liver tissue and SCH, consistent with efficient hepatic uptake. Despite extensive binding and sequestration of furamidine within liver tissue, a significant portion of cellular accumulation was attributed to unbound drug (Kpu,u >16), as expected for a charged, hepatically derived metabolite. Data demonstrate the utility of SCH to predict quantitatively total tissue accumulation and elucidate mechanisms of hepatocellular drug accumulation such as active uptake versus binding/sequestration.

41 citations

Journal ArticleDOI
TL;DR: Current knowledge about the impact of transporter proteins on drug availability within pharmacologically relevant cellular compartments and tissues as hepatocytes, enterocytes, different blood cell types, brain, and the heart are summarized with emphasis on the potential clinical significance of these transporters.
Abstract: Active transport across biological membranes represents a critical step in the disposition of many drugs. It is now well-established that different efflux and uptake transporters such as P-glycoprotein (P-gp), multidrug resistance-associated proteins (MRPs) or organic anion transporting polypeptides (OATPs) are involved in the overall disposition and efficacy of numerous compounds. These proteins are mainly expressed at physiological sites of drug absorption and elimination, thus leading to diminished absorption and/or increased transporter-facilitated excretion. Moreover, drug transporters are known to be of protective significance in blood-organ barriers. On the contrary, only little is known about the relevance of transporter function on drug levels within tissues and cellular compartments, i.e. the site of action for many substances. Moreover, the pharmacokinetic processing inside the cell is characterized by uptake, metabolism and elimination. It is gradually being recognized that active uptake and/or efflux transporters may modify target concentrations at the subcellular receptor sites which in turn may have an influence on drug effects. This review will summarize current knowledge about the impact of transporter proteins on drug availability within pharmacologically relevant cellular compartments and tissues as hepatocytes, enterocytes, different blood cell types, brain, and the heart with emphasis on the potential clinical significance of these transporters.

40 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20237
202225
202133
202040
201933
201829