@article{PreisingSchneiderBucheretal.2015,
  author    = {Preising, Christina and Schneider, Reinhard and Bucher, Michael and Gekle, Michael and Sauvant, Christoph},
  title     = {Regulation of expression of renal organic anion transporters OAT1 and OAT3 in a model of ischemia/reperfusion injury},
  series = {Cellular Physiology and Biochemistry},
  volume    = {37},
  journal   = {Cellular Physiology and Biochemistry},
  number    = {1},
  doi       = {10.1159/000430328},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144504},
  year      = {2015},
  abstract  = {Background: Recently, we gained evidence that impairment of rOat1 and rOat3 expression induced by ischemic acute kidney injury (AKI) is mediated by COX metabolites and this suppression might be critically involved in renal damage. Methods: (i) Basolateral organic anion uptake into proximal tubular cells after model ischemia and reperfusion (I/R) was investigated by fluorescein uptake. The putative promoter sequences from hOAT1 (SLC22A6) and hOAT3 (SCL22A8) were cloned into a reporter plasmid, transfected into HEK cells and (ii) transcriptional activity was determined after model ischemia and reperfusion as a SEAP reporter gen assay. Inhibitors or antagonists were applied with the beginning of reperfusion. Results: By using inhibitors of PKA (H89) and PLC (U73122), antagonists of E prostanoid receptor type 2 (AH6809) and type 4 (L161,982), we gained evidence that I/R induced down regulation of organic anion transport is mediated by COX1 metabolites via E prostanoid receptor type 4. The latter signaling was confirmed by application of butaprost (EP2 agonist) or TCS2510 (EP4 agonist) to control cells. In brief, the latter signaling was verified for the transcriptional activity in the reporter gen assay established. Therein, selective inhibitors for COX1 (SC58125) and COX2 (SC560) were also applied. Conclusion: Our data show (a) that COX1 metabolites are involved in the regulation of renal organic anion transport(ers) after I/R via the EP4 receptor and (b) that this is due to transcriptional regulation of the respective transporters. As the promoter sequences cloned were of human origin and expressed in a human renal epithelial cell line we (c) hypothesize that the regulatory mechanisms described after I/R is meaningful for humans as well.},
  language  = {en}
}
@article{FrerichsSirenFeuersteinetal.1992,
  author    = {Frerichs, K. and Sir{\`e}n, Anna-Leena and Feuerstein, G. and Hallenbeck, JM},
  title     = {The onset of postischemic hypoperfusion in rats is precipitous and may be controlled by local neurons},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-47980},
  year      = {1992},
  abstract  = {Background and Purpose: Reperfusion following transient global cerebral ischemia is characterized by an initial hyperemic phase, which precedes hypo perfusion. The pathogenesis of these flow derangements remains obscure. Our study investigates the dynamics of postischemic cerebral blood flow changes, with particular attention to the role of local neurons. Metho(Js: We assessed local cortical blood flow continuously by laser Doppler flowmetry to permit observation of any rapid flow changes after forebrain ischemia induced by four-vessel occlusion for 20 minutes in rats. To investigate the role of local cortical neurons in the regulation of any blood flow fluctuations, five rats received intracortical microinjections of a neurotoxin (10 p,g ibotenic acid in 1 p,1; 1.5-mm-depth parietal cortex) 24 hours before ischemia to induce selective and localized neuronal depletion in an area corresponding to the sampie volume of the laser Doppler probe (1 mm3 ). Local cerebral blood flow was measured within the injection site and at an adjacent control site. Results: Ischemia was followed by marked hyperemia (235 ±23\% of control, n =7), followed by secondary hypoperfusion (45±3\% of control, n=7). The transition from hyperemia to hypoperfusioo occurred not gradually but precipitously (maximal slope of flow decay: 66±6\%/min; n=7). In ibotenic acid-injected rats, hyperemia was preserved at the injection site, but the sudden decline of blood flow was abolished (maximal slope of flow decay: 5±3\%/min compared with 53±8\%/min at the control site; n=5, p<O.OOI) and 00 significant hypoperfusion de\eloped (103±20\% of control at 60 minutes). Conclusions: These data suggest that the rapid transition to cortical hypo perfusion after forebrain ischemia may be triggered locally by a neuronal mechanism but that this mechanism does not underlie the initial hyperemia.},
  subject      = {Gehirn},
  language  = {en}
}