Apical Expression or Expression in a Non Polarized Cell of hOAT1 Inverses Regulation by Epidermal Growth Factor (EGF) as Compared to Basolateral hOAT1

Hesse, D; Sauvant, Christoph; Holzinger, Hildegard; Gekle, Michael

doi:10.1159/000078109

Cited by 14 publications

(7 citation statements)

References 40 publications

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“…Despite this, a minority of patients treats their disease, reflected in a low impact on DLQI. Lack of treatment may be due to poor treatment satisfaction as only 40% of those who ever treated their disease were satisfied compared to 60% in previous studies [6, 21]. It can be expected that patients who are more disappointed by medical treatments volunteer to evaluate the use of camouflage.…”

Section: Discussionmentioning

confidence: 98%

Quality of Life and Stigmatization Profile in a Cohort of Vitiligo Patients and Effect of the Use of Camouflage

Ongenae¹,

Dierckxsens²,

Brochez³

et al. 2005

Dermatology

164

154

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Background: Few studies have paid attention to the effects of treatment interventions on the psychosocial consequences of vitiligo. Objectives: To quantify and analyse the psychosocial benefit of the use of camouflage in vitiligo patients. Patients and Methods: 78 vitiligo patients completed the Dermatology Life Quality Index (DLQI) and an adapted stigmatization questionnaire, and 62 of them completed the DLQI after at least a 1-month use of camouflage. Results: The initial mean overall DLQI score (n = 78) is 6.9 (SD 5.6). The mean global stigmatization score is 38%. Disease extent and disease severity are strong predictors of the DLQI (p < 0.0001). Vitiligo on the face/head/neck substantially affects the DLQI, independently of degree of involvement. The mean DLQI score before and after use of camouflage (n = 62) is 7.3 (SD 5.6) and 5.9 (SD 5.2; p = 0.006). Mainly the high-scoring items ‘feelings of embarrassment and self consciousness’ and ‘choice of clothing’ improve. Predictors of improvement are higher DLQI scores (p = 0.0005) and higher total severity scores (p = 0.03). Conclusions: Camouflage can be recommended, particularly in patients with higher DLQI scores or self-assessed disease severity. Patients with minor involvement of the face benefit from camouflage.

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Section: Discussionmentioning

confidence: 98%

Quality of Life and Stigmatization Profile in a Cohort of Vitiligo Patients and Effect of the Use of Camouflage

Ongenae¹,

Dierckxsens²,

Brochez³

et al. 2005

Dermatology

164

154

View full text Add to dashboard Cite

show abstract

“…Perhaps less controversial is the influence of EGF on OAT function, as several other studies supported the findings mentioned above, either for OAT1 or OAT3. In one of these studies, EGF stimulated basolateral fluorescein uptake into a hOAT1-expressing human renal epithelial cell line (IHKE-hOAT1) [110]. Interestingly, when assessed in non-polarized Chinese hamster ovary (CHO) cells, EGF instead decreased fluorescein uptake [110].…”

Section: Phosphorylationmentioning

confidence: 99%

“…In one of these studies, EGF stimulated basolateral fluorescein uptake into a hOAT1-expressing human renal epithelial cell line (IHKE-hOAT1) [110]. Interestingly, when assessed in non-polarized Chinese hamster ovary (CHO) cells, EGF instead decreased fluorescein uptake [110]. This finding suggested that EGF may have stimulatory effects in healthy renal cells, but inhibitory effects in damaged/nonpolarized renal cells.…”

Section: Phosphorylationmentioning

confidence: 99%

Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiology

VanWert

Gionfriddo

Sweet

2009

Biopharm & Drug Disp

222

238

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Our understanding of the mechanisms behind inter-and intra-patient variability in drug response is inadequate. Advances in the cytochrome P450 drug metabolizing enzyme field have been remarkable, but those in the drug transporter field have trailed behind. Currently, however, interest in carrier-mediated disposition of pharmacotherapeutics is on a substantial uprise. This is exemplified by the 2006 FDA guidance statement directed to the pharmaceutical industry. The guidance recommended that industry ascertain whether novel drug entities interact with transporters. This suggestion likely stems from the observation that several novel cloned transporters contribute significantly to the disposition of various approved drugs. Many drugs bear anionic functional groups, and thus interact with organic anion transporters (OATs). Collectively, these transporters are nearly ubiquitously expressed in barrier epithelia. Moreover, several reports indicate that OATs are subject to diverse forms of regulation, much like drug metabolizing enzymes and receptors. Thus, critical to furthering our understanding of patient-and condition-specific responses to pharmacotherapy is the complete characterization of OAT interactions with drugs and regulatory factors. This review provides the reader with a comprehensive account of the function and substrate profile of cloned OATs. In addition, a major focus of this review is on the regulation of OATs including the impact of transcriptional and epigenetic factors, phosphorylation, hormones and gender.

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“…Western blot analysis was done as described previously (29). Cells on Petri dishes were rinsed three times with PBS.…”

Section: Western Blot Analysismentioning

confidence: 99%

Prostaglandin E2 Inhibits Its Own Renal Transport by Downregulation of Organic Anion Transporters rOAT1 and rOAT3

Sauvant¹,

Holzinger²,

Gekle³

2006

Journal of the American Society of Nephrology

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Prostaglandin E 2 (PGE 2 ) is the principal mediator of fever and inflammation. Recently, evidence emerged that during febrile response, PGE 2 that is generated in the periphery enters the hypothalamus and contributes to the maintenance of fever. In a rat model of fever generation, peripheral PGE 2 is increased, whereas clearance by metabolism of peripheral PGE 2 is downregulated. The major route of PGE 2 excretion is via the renal proximal tubular organic anion secretory system, where basolateral uptake that is mediated by renal organic anion transporter 1 (rOAT1) and rOAT3 is rate limiting. Therefore, it was hypothesized that PGE 2 itself will abolish its excretion by rOAT1 or rOAT3. Fluorescein was used as a prototypic organic anion, and NRK-52E cells from rat served as a proximal tubular model system. PGE 2 time-dependently downregulates basolateral organic anion uptake, without affecting cell volume or cell protein, recirculation of counter ions, or proximal tubular transport systems in general. In addition, PGE 2 diminishes expression of both rOAT1 and rOAT3. Both organic anion uptake and expression of rOAT1 and rOAT3 are dose-dependently downregulated by PGE 2 . These findings suggest that during fever or inflammation, renal secretory transport of PGE 2 is reduced, contributing to elevated PGE 2 levels in blood. These data fit into the hypothetical concept of peripheral PGE 2 's playing a significant role in fever. The described regulatory mechanism may also be of relevance in chronic inflammatory events. Moreover, the data presented could explain why increased plasma urate levels occur in diseases that go along with increased levels of PGE 2 .J Am Soc Nephrol 17: 46 -53, 200646 -53, . doi: 10.1681 T he organic anion transport system of the renal proximal tubule plays a crucial role in the excretion of a variety of potentially toxic compounds. This system consists of organic anion exchangers that are located at the basolateral membrane and a less well-characterized transport step at the apical membrane. The classical basolateral organic anion exchanger is the terminal step in a tertiary active transport system, dependent on an inward-directed Na ϩ gradient to drive the uptake of ␣-ketoglutarate, which then is exchanged for organic anions. It has been shown that OAT1 represents characteristics of the basolateral, polyspecific transporter for organic anions, which had been functionally described for some time (1). Recently, new evidence has indicated that organic anion transporter 3 (OAT3) (2), which also is located in the basolateral renal proximal tubular membrane, also works as an appropriate exchanger for organic anions and dicarboxylates (3,4). Moreover, additional homologues have been cloned and were called OAT2 (5), OAT4 (6), OAT5 (7), and OAT6 (8). These clones show 40 to 60% homology in amino acid sequence compared with OAT1 or OAT3, and they differ in substrate specificity and expression pattern. Furthermore, these latter proteins are not anion exchangers like OAT1 or OAT3 but seem to work as fac...

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Apical Expression or Expression in a Non Polarized Cell of hOAT1 Inverses Regulation by Epidermal Growth Factor (EGF) as Compared to Basolateral hOAT1

Cited by 14 publications

References 40 publications

Quality of Life and Stigmatization Profile in a Cohort of Vitiligo Patients and Effect of the Use of Camouflage

Quality of Life and Stigmatization Profile in a Cohort of Vitiligo Patients and Effect of the Use of Camouflage

Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiology

Prostaglandin E2 Inhibits Its Own Renal Transport by Downregulation of Organic Anion Transporters rOAT1 and rOAT3

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