Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The C57BL/6J-cpk mouse has a form of autosomal-recessive polycystic kidney disease characterized by the rapid growth of large collecting duct cysts and the development of severe renal failure usually by three to four weeks of age. Previous studies had shown higher steady-state levels of proto-oncogene mRNA in these cystic kidneys. It is now shown using nuclear run-on transcription that the c-fos and c-myc proto-oncogenes are transcribed at higher rates in cystic kidneys, and thus that increased transcription, in part, may account for the increased mRNA levels. c-myc mRNA was detected by in situ hybridization in nephron anlagen and elongating tubules of normal and cystic kidneys during late fetal and early neonatal kidney development. Localization of c-myc expression in the normal kidney decreased with age over the three-week postnatal period. By contrast, c-myc mRNA was found in cysts as early as three days of age, with increased levels at two and three weeks. c-myc expression was also elevated in apparently normal, non-dividing proximal tubules in three-week-old cystic animals. On the basis of these findings, we suggest that c-myc expression is linked to the proliferation of cells engaged in the primary cystogenic process, and that expression of this gene in proximal tubule cells of severely azotemic animals reflects the compensatory response of residual tubular epithelial cells to progressive renal dysfunction.
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PMID:Localization of overexpressed c-myc mRNA in polycystic kidneys of the cpk mouse. 155 5

The response of the kidney to ischemic injury includes increased DNA synthesis, which is preceded by rapid and brief expression of the c-fos proto-oncogene. While the timing of these two events would suggest that c-Fos participates in an immediate-early gene program leading to proliferation, no direct test of this hypothesis exists. The purpose of these studies was (1) to determine whether c-fos is expressed as part of a typical immediate-early (IE) gene response, which would require co-expression of c-jun and sensitivity to cycloheximide, and (2) to determine whether the cells expressing c-Fos are the same as those undergoing DNA synthesis. Northern analysis was performed on renal mRNA at different times following release of a 50 minute period of renal hilar clamping. c-jun and c-fos mRNA were rapidly and briefly expressed following renal ischemia and their expression was superinduced by cycloheximide in a manner typical of an immediate-early gene response. 3H-thymidine autoradiography performed on semi-thin sections from intravascularly perfusion fixed kidneys 24 hours following induction of ischemia showed labeled nuclei in cells lining the damaged proximal tubules of the outer stripe of the outer medulla, as well as proximal tubules in the cortex and interstitial cells throughout the kidney. However, immunohistochemical localization of c-Fos and c-Jun protein occurred predominantly in nuclei of the thick ascending limb, distal tubule and collecting duct cells. The studies demonstrate that c-fos and c-jun are expressed following renal ischemia as a typical immediate-early gene response, but they are expressed in cells that do not enter the cell cycle. The failure of the cells to enter the cell cycle may depend on the co-expression of jun-B and jun-D, which suppress the mitogenic activity of c-Jun in other cells. The data suggest that the IE response following renal ischemia is part of the stress response, which is antiproliferative rather than proliferative. The role of the stress response during renal ischemia and the fate of the cells undergoing it are unknown.
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PMID:DNA synthesis is dissociated from the immediate-early gene response in the post-ischemic kidney. 854 1

We have previously demonstrated that cisplatin-induced nephrotoxicity is associated with the induction of apoptosis using mouse renal cells derived from the terminal proximal tubule (S3) which is the major target site of cisplatin-induced injury. The purpose of this study was to elucidate the intracellular mechanisms leading to the cisplatin-induced apoptosis of S3 cells. Actinomycin D (an inhibitor of RNA synthesis), cycloheximide (an inhibitor of protein synthesis) and aurintricarboxylic acid (an endonuclease inhibitor) reduced the extent of DNA fragmentation, a biochemical parameter of apoptosis, in cisplatin-treated S3 cells. Furthermore, cisplatin-induced apoptosis of S3 cells was accompanied by an increase in the level of c-fos mRNA expression, which is inhibited by pretreatment of the cells with actinomycin D, but not with cycloheximide or aurintricarboxylic acid. In contrast, outer medullary collecting duct cells treated with cisplatin exhibited morphological changes characteristic of apoptosis and an increase in the level of c-fos mRNA expression, but no increase in the extent of DNA fragmentation. In conclusion, the synthesis of macromolecules such as RNA and protein, endonuclease activation and c-fos expression appear to be involved in the intracellular pathways leading to the induction of apoptosis in cisplatin-treated S3 cells. In addition, the response to cisplatin may be different in different cells.
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PMID:Involvement of macromolecule synthesis, endonuclease activation and c-fos expression in cisplatin-induced apoptosis of mouse proximal tubule cells. 957 5

Low sensitivity is characteristic of many proteomics methods. Presented here is an approach that combines proteomics based on difference gel electrophoresis (DIGE) with bioinformatic pathways analysis to identify both abundant and relatively nonabundant proteins in inner medullary collecting duct (IMCD) altered in abundance during escape from vasopressin-induced antidiuresis. Rats received the vasopressin analog dDAVP by osmotic minipump plus either a daily water load (vasopressin escape) or only enough water to replace losses (control). Immunoblotting confirmed the hallmark of vasopressin escape, a decrease in aquaporin-2, and demonstrated a decrease in the abundance of the urea transporter UT-A3. DIGE identified 22 mostly high-abundance proteins regulated during vasopressin escape. These proteins were analyzed using pathways analysis software to reveal protein clusters incorporating the proteins identified by DIGE. A single dominant cluster emerged that included many relatively low-abundance proteins (abundances too low for DIGE identification), including several transcription factors. Immunoblotting confirmed a decrease in total and phosphorylated c-myc, a decrease in c-fos, and increases in c-jun and p53. Furthermore, immunoblotting confirmed hypothesized changes in other proteins in the proposed network: Increases in c-src, receptor for activated C kinase 1, calreticulin, and caspase 3 and decreases in steroid receptor co-activator 1, Grp78/BiP, and annexin A4. This combined approach proved capable of uncovering regulatory proteins that are altered in response to a specific physiologic perturbation without being detected directly by DIGE. The results demonstrate a dominant protein regulatory network in IMCD cells that is altered in association with vasopressin escape, providing a new framework for further studies of signaling in IMCD.
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PMID:Combined proteomics and pathways analysis of collecting duct reveals a protein regulatory network activated in vasopressin escape. 1607 66