Changes in phosphorylated heat‐shock protein 27 in response to acute ureteral obstruction in rats

Carlsen, Inge; Nilsson, Line; Frøkiær, Jørgen; Nørregaard, Rikke

doi:10.1111/apha.12135

Cited by 5 publications

(6 citation statements)

References 36 publications

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“…We have previously shown that phosphorylated HSP27 was increased in response to 6-and 12-h UUO (5). Our data also demonstrated the induction of phosphorylated HSP27 and HSP32 after 24-h UUO.…”

Section: Discussionsupporting

confidence: 84%

“…Previous studies have demonstrated that quercetin reduces the expression of HSPs (12). We (5) have previously shown induction of the phosphorylated form of HSP27 after 6-and 12-h UUO, and another study (1) has shown that HSP27 is required for induction of COX-2. Therefore, the effects of quercetin on HSP27, phosphorylated HSP27, HSP32, and HSP70 expression in the IM in response to 24-h UUO were examined.…”

Section: Quercetin Attenuated Cox-2 Induction In the Renal Im In Respmentioning

confidence: 57%

“…The effect of stretch on RMICs was studied using the Flexcell FX-5000T system (Dunn Labortechnik, Asbach, Germany), which applies stretch to adhering cell types. RMICs were cultured on collagen-coated BioFlex six-well plates (Dunn Labortechnik) and exposed to 20% uniform static stretch for 4 h. The determination of optimal stretch conditions was performed as previously described by Carlsen et al (5). Cells not subjected to stretch were used as controls.…”

Section: Methodsmentioning

confidence: 99%

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Quercetin attenuates cyclooxygenase-2 expression in response to acute ureteral obstruction

Carlsen

Frøkiær

Nørregaard

2015

American Journal of Physiology-Renal Physiology

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Unilateral ureteral obstruction (UUO) is associated with increased hydrostatic pressure, inflammation, and oxidative stress in the renal parenchyma. Previous studies have demonstrated marked cyclooxygenase (COX)-2 induction in renal medullary interstitial cells (RMICs) in response to UUO. The aim of the present study was to evaluate the effect of quercetin, a naturally occurring antioxidant, on COX-2 induction in vivo and in vitro. Rats subjected to 24 h of UUO were treated intraperitoneally with quercetin (50 mg·kg(-1)·day(-1)). Quercetin partly prevented COX-2 induction in the renal inner medulla in response to UUO. Moreover, RMICs exposed to conditions associated with obstruction, inflammation (produced by IL-1β), oxidative stress (produced by H2O2), and mechanical stress (produced by stretch) showed increased COX-2 expression. Interestingly, quercetin reduced COX-2 induction in RMICs subjected to stretched. Similarly, PGE2 production was markedly increased in RMICs exposed to stretch and was reversed to control levels by quercetin treatment. Furthermore, stretch-induced phosphorylation of ERK1/2 was blocked by quercetin, and inhibition of ERK1/2 attenuated stretch-induced COX-2 induction in RMICs. These results indicate that quercetin attenuated the induction of COX-2 expression and activity in RMICs exposed to mechanical stress as a consequence of acute UUO and that the MAPK ERK1/2 pathway might be involved in this quercetin-mediated reduction in COX-2.

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Section: Discussionsupporting

confidence: 84%

Section: Quercetin Attenuated Cox-2 Induction In the Renal Im In Respmentioning

confidence: 57%

Section: Methodsmentioning

confidence: 99%

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Quercetin attenuates cyclooxygenase-2 expression in response to acute ureteral obstruction

Carlsen

Frøkiær

Nørregaard

2015

American Journal of Physiology-Renal Physiology

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“…Salinthone et al [2007] demonstrated that Hsp27 inhibited this proliferation by affecting the rate of proliferation, not by halting the cell cycle progres- sion once the cell enters the cycle . So, Hsp27 is thought to have cytoprotective effects, promote reorganization of actin filaments and stabilize fibers when cells are exposed to oxidative stress [Huot et al, 1996;Carlsen et al, 2013].…”

Section: Discussionmentioning

confidence: 99%

Comparative Proteome Analyses of Ureteropelvic Junction Obstruction and Surrounding Ureteral Tissue

Görmüş

Kasap

Akpınar

et al. 2020

Cells Tissues Organs

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Ureteropelvic junction (UPJ) obstruction is a common problem in children, but its etiology remains unclear. In this study, the proteome profiles of the obstructed segment and its surrounding distal and proximal parts were comparatively evaluated. Twelve children younger than 2 years of age with unilateral intrinsic UPJ obstruction were included. The excised operational tissue was divided into three parts immediately after resection: the obstructed part (Obst), the distal normal ureteral part (Dist), and the proximal part of the obstructed segment (Prox). Proteins extracted from the tissue samples were subjected to two-dimensional gel electrophoresis analysis to identify differentially regulated proteins. Spot analysis revealed that four proteins, namely tropomyosin beta and alpha-1 chains, actin and desmin, were upregulated in Obst in comparison to Dist. A similar analysis between Obst and Prox showed that heat shock protein beta-1 and carbonic anhydrase-1 were upregulated in Obst, while tropomyosin alpha 3 chain and ATP synthase beta were upregulated in Prox. The last comparative analysis between Dist and Prox revealed upregulation of annexin-A5 and annexin-A1 in Dist and vimentin, mitochondrial ATP synthase subunit-beta, peroxiredoxin-2, and apolipoprotein-A1 in Prox. Bioinformatics analysis using the STRING server indicated that the differentially regulated proteins, altogether, point to the changes occurring in muscle filament sliding pathway. When regulations occurring in each group were mutually compared, a change in lipase inhibition activity was detected by STRING. This is the first study scrutinizing changes occurring in protein profiles in UPJ.

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“…The acute increases in intrarenal pressure are suggested to impact the tubular epithelial cells by mechanical stretch due to tubular distention. Changes in specific antioxidant enzymes and stress proteins in in vivo models of obstruction can be retrieved from the in vitro model of cells subjected to mechanical stress (8,40). Furthermore, it was recently shown that the inflammatory protein cyclooxygenase 2 increases in in vivo models of UUO and BUO (11,34) and in an in vitro cell model where renal medullary interstitial cells were subjected to 60-mmHg pressure for 6 h (7).…”

Section: Discussionmentioning

confidence: 99%

Proteomic identification of early changes in the renal cytoskeleton in obstructive uropathy

Stødkilde

Palmfeldt

Nilsson

et al. 2014

American Journal of Physiology-Renal Physiology

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Bilateral ureteral obstruction (BUO) is associated with renal damage and impaired ability to concentrate urine and is known to induce alterations in an array of kidney proteins. The aim of this study was to identify acute proteomic alterations induced by BUO. Rats were subjected to BUO for 2, 6, or 24 h. Mass spectrometry-based proteomics was performed on the renal inner medulla, and protein changes in the obstructed group were identified. Significant changes were successfully identified for 109 proteins belonging to different biological classes. Interestingly, proteins belonging to the cytoskeleton and proteins related to cytoskeletal regulation were found to be biologically enriched in BUO using online-accessible tools. Western blots confirmed the selected results, demonstrating acute downregulation of proteins belonging to all three cytoskeletal components. The microfilament protein β-actin and the intermediate filament proteins pankeratin and vimentin were all downregulated. β-Tubulin, an important microtubular protein, was found to be significantly downregulated after 24 h. Also, there was significant upregulation of cofilin, an actin-binding protein known to be upregulated in other nephropathy models. Furthermore, both upregulation and downregulation of cytoskeletal motor and regulatory proteins were observed. These findings were confirmed by immunohistochemistry, which clearly showed alterations in labeling in the inner medulla. Interestingly, we were able to confirm selected results in mpkCCD cells exposed to mechanical stretch. Our findings add to the knowledge of BUO-induced acute changes in the renal cytoskeleton and suggest that these molecular changes are partly mediated by increased stretch of the cells during obstruction.

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Changes in phosphorylated heat‐shock protein 27 in response to acute ureteral obstruction in rats

Abstract: These data demonstrate that, in response to acute UUO, different forms of cellular stresses modulate HSP27 expression and phosphorylation in RMICs. This may affect the ability of renal cells to mount an effective cytoprotective response.

Cited by 5 publications

References 36 publications

Quercetin attenuates cyclooxygenase-2 expression in response to acute ureteral obstruction

Quercetin attenuates cyclooxygenase-2 expression in response to acute ureteral obstruction

Comparative Proteome Analyses of Ureteropelvic Junction Obstruction and Surrounding Ureteral Tissue

Proteomic identification of early changes in the renal cytoskeleton in obstructive uropathy

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