Tin protoporphyrin induces intestinal chloride secretion by inducing light oxidation processes

Uç, Aliye; Reszka, Krzysztof J.; Buettner, Garry R.; Stokes, John B.

doi:10.1152/ajpcell.00550.2006

Cited by 6 publications

(5 citation statements)

References 49 publications

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“…The statin-dependent inhibition of PGE 2 in the air pouch in mice confirmed our previous results in cultured human monocytes [21]. SnPPIX has been widely used as an HO-1 inhibitor with success [52–54] despite few HO-1 independent reports [55, 56].…”

Section: Discussionsupporting

confidence: 84%

Heme oxygenase-1—Dependent anti-inflammatory effects of atorvastatin in zymosan-injected subcutaneous air pouch in mice

et al. 2019

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Statins exert pleiotropic and beneficial anti-inflammatory and antioxidant effects. We have previously reported that macrophages treated with statins increased the expression of heme oxygenase-1 (HO-1), an inducible anti-inflammatory and cytoprotective stress protein, responsible for the degradation of heme. In the present study, we investigated the effects of atorvastatin on inflammation in mice and analyzed its mechanism of action in vivo . Air pouches were established in 8 week-old female C57BL/6J mice. Atorvastatin (5 mg/kg, i.p.) and/or tin protoporphyrin IX (SnPPIX), a heme oxygenase inhibitor (12 mg/kg, i.p.), were administered for 10 days. Zymosan, a cell wall component of Saccharomyces cerevisiae, was injected in the air pouch to trigger inflammation. Cell number and levels of inflammatory markers were determined in exudates collected from the pouch 24 hours post zymosan injection by flow cytometry, ELISA and quantitative PCR. Analysis of the mice treated with atorvastatin alone displayed increased expression of HO-1, arginase-1, C-type lectin domain containing 7A, and mannose receptor C-type 1 in the cells of the exudate of the air pouch. Flow cytometry analysis revealed an increase in monocyte/macrophage cells expressing HO-1 and in leukocytes expressing MRC-1 in response to atorvastatin. Mice treated with atorvastatin showed a significant reduction in cell influx in response to zymosan, and in the expression of proinflammatory cytokines and chemokines such as interleukin-1α, monocyte chemoattractant protein-1 and prostaglandin E 2 . Co-treatment of mice with atorvastatin and tin protoporphyrin IX (SnPPIX), an inhibitor of heme oxygenase, reversed the inhibitory effect of statin on cell influx and proinflammatory markers, suggesting a protective role of HO-1. Flow cytometry analysis of air pouch cell contents revealed prevalence of neutrophils and to a lesser extent of monocytes/macrophages with no significant effect of atorvastatin treatment on the modification of their relative proportion. These findings identify HO-1 as a target for the therapeutic actions of atorvastatin and highlight its potential role as an in vivo anti-inflammatory agent.

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Section: Discussionsupporting

confidence: 84%

Heme oxygenase-1—Dependent anti-inflammatory effects of atorvastatin in zymosan-injected subcutaneous air pouch in mice

et al. 2019

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“…Unless otherwise indicated, all measurements were made at 37°C in growth medium equilibrated to room air (20% O 2). In experiments in which we tested the effect of tin protoporphyrin (SnPP) on I sc, we kept the solutions and monolayers in the dark to prevent light activation of SnPP, which can produce potent biological effects (52). For all experiments involving nonelectrical measurements, we measured the I sc and Rt of the 12-mm monolayers before making the biochemical determination.…”

Section: Methodsmentioning

confidence: 99%

“…5B, protein abundance of HO-1 was significantly lower at higher concentrations of O 2 , but there was no difference between 8 and 20%. We also tested the ability of SnPP, an inhibitor of heme oxygenase (52), to alter the effects of varying O 2 ; there was no effect (Fig. 5C).…”

Section: Effects Of O 2 and Corticosteroids On Na Transportmentioning

confidence: 99%

Oxygen regulation of the epithelial Na channel in the collecting duct

Husted

Sigmund

et al. 2011

American Journal of Physiology-Renal Physiology

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The PO 2 within the kidney changes dramatically from cortex to medulla. The present experiments examined the effect of changing PO 2 on epithelial Na channel (ENaC)-mediated Na transport in the collecting duct using the mpkCCD-c14 cell line. Decreasing ambient O 2 concentration from 20 to 8% decreased ENaC activity by 40%; increasing O2 content to 40% increased ENaC activity by 50%. The O 2 effect required several hours to develop and was not mimicked by the acid pH that developed in monolayers incubated in low-O2 medium. Corticosteroids increased ENaC activity at each O 2 concentration; there was no interaction. The pathways for O2 and steroid regulation of ENaC are different since O2 did not substantially affect Sgk1, ␣-ENaC, Gilz, or Usp2-45 mRNA levels, genes involved in steroid-mediated ENaC regulation. The regulation of ENaC activity by these levels of O2 appears not to be mediated by changes in hypoxia-inducible factor-1␣ or -2␣ activity or a change in AMP kinase activity. Changes in O2 concentration had minimal effect on ␣-or ␥-ENaC mRNA and protein levels; there were moderate effects on ␤-ENaC levels. However, 40% O2 induced substantially greater total ␤-and ␥-ENaC on the apical surface compared with 8% O2; both subunits demonstrated a greater increase in the mature forms. The ␣-ENaC subunit was difficult to detect on the apical surface, perhaps because our antibodies do not recognize the major mature form. These results identify a mechanism of ENaC regulation that may be important in different regions of the kidney and in responses to changes in dietary NaCl.heat shock protein-70; heme oxygenase; adenosine 5=-monophosphate kinase; hypoxia-inducible factor-1␣; corticosteroids; surface expression THE OXYGEN TENSION OF THE renal parenchyma varies from that approaching the PO 2 of arterial blood near the surface of the kidney to considerably lower values in the midcortex (35). The PO 2 of the inner medulla is substantially below that of almost all normal tissues with values of 10 -15 Torr being routinely measured (4, 35). The relatively low PO 2 in both the cortex and the medulla is the result of a functional countercurrent exchange between arterioles and venules. The lower PO 2 in the medulla is believed to predispose to tubular injury in the setting of acute hemodynamic compromise, but the physiological consequences of the widely varying PO 2 of different regions is poorly understood.The collecting duct traverses the axis of the kidney from cortex to papillary tip and, consequently, is exposed to a wide range of PO 2 . It is well known that the rate of Na absorption by the cortical collecting duct is considerably greater than that by the medullary collecting duct (19,48). The reason for this regional difference in Na transport rate is not clear. Two possibilities have been proposed: hypertonicity and the high concentration of transforming growth factor-␤ within the renal medulla (28). Another possibility is the O 2 tension: low PO 2 in lung epithelial cells reduces epithelial Na channel (ENaC) activity (...

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“…HG-induced EMT, 50 µM SnPP, a known inhibitor of HO, was utilized. The concentration of SnPP was determined as previously described(49). As shown inFig.…”

mentioning

confidence: 99%

Curcumin protects renal tubular epithelial cells from high glucose-induced epithelial-to-mesenchymal transition through Nrf2-mediated upregulation of heme oxygenase-1

Zhang

Liang

Guo

et al. 2012

Molecular Medicine Reports

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Curcumin has been observed to exhibit an anti-fibrotic effect in the liver, lung and gallbladder. However, the mechanisms underlying the cytoprotective effects of curcumin remain to be elucidated. The epithelial-to-mesenchymal transition (EMT) of mature tubular epithelial cells in the kidney is considered to contribute to the renal accumulation of matrix proteins associated with diabetic nephropathy. The EMT is also closely associated with the progression of renal interstitial fibrosis and oxidative stress. This process may occur through abrogation of high glucose (HG)-induced oxidative stress via activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1 (HO-1) in kidney tubular epithelial cells. In the present study, the effect of curcumin on HG-induced EMT in the NRK-52E normal rat kidney tubular epithelial cell line was investigated, and whether the effect of curcumin was mediated by the induction of Nrf2 and HO-1 expression was examined. The present study revealed that curcumin was able to prevent events associated with EMT, including the downregulation of E-cadherin and the increased expression of α-smooth muscle actin. Further analysis revealed that the expression levels of Nrf2 and HO-1 protein were elevated to a greater extent in the curcumin pretreated NRK-52E cells compared with those of the control. Notably, knockdown of Nrf2 with small interfering RNA prevented the curcumin-induced elevation in expression of HO-1 and the associated anti-fibrotic effects. In conclusion, the present findings suggested that curcumin may be significant in cellular antioxidant defense, through the activation of Nrf2 and HO-1, thereby protecting the NRK-52E cells from HG-induced EMT.

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Tin protoporphyrin induces intestinal chloride secretion by inducing light oxidation processes

Cited by 6 publications

References 49 publications

Heme oxygenase-1—Dependent anti-inflammatory effects of atorvastatin in zymosan-injected subcutaneous air pouch in mice

Heme oxygenase-1—Dependent anti-inflammatory effects of atorvastatin in zymosan-injected subcutaneous air pouch in mice

Oxygen regulation of the epithelial Na channel in the collecting duct

Curcumin protects renal tubular epithelial cells from high glucose-induced epithelial-to-mesenchymal transition through Nrf2-mediated upregulation of heme oxygenase-1

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