Oxidative signaling in renal epithelium: Critical role of cytosolic phospholipase A2 and p38SAPK

Cui, Xiao; Ding, Yaxian; Alexander, Larry D.; Bao, Chengyuan; Al‐Khalili, Otor; Simonson, Michael S.; Eaton, Douglas C.; Douglas, Janice G.

doi:10.1016/j.freeradbiomed.2006.02.004

Cited by 24 publications

(20 citation statements)

References 45 publications

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“…These data suggest differences in AT2 receptor coupling in ARPE-19 cells. AT2 receptor could be specifically coupled to the cytosolic phospholipase A 2 (cPLA 2 ), as has been shown recently in renal mesangial and proximal tubular epithelium cells, and not to the PLC pathway (15). Therefore, selective up-or downregulation of only AT2 receptor transduction pathway remains a possibility to be investigated.…”

Section: Discussionmentioning

confidence: 98%

Regulation of angiotensin II receptors and extracellular matrix turnover in human retinal pigment epithelium: role of angiotensin II

Striker

Praddaude

Garnica

et al. 2008

American Journal of Physiology-Cell Physiology

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Striker GE, Praddaude F, Alcazar O, Cousins SW, MarinCastañ o ME. Regulation of angiotensin II receptors and extracellular matrix turnover in human retinal pigment epithelium: role of angiotensin II. Am J Physiol Cell Physiol 295: C1633-C1646, 2008. First published October 15, 2008 doi:10.1152/ajpcell.00092.2008.-The early stage of age-related macular degeneration (AMD) is characterized by the formation of subretinal pigment epithelium (RPE) deposits as a result of the dysregulation in the turnover of extracellular matrix (ECM) molecules. However, the mechanism involved remains unclear. Hypertension (HTN) is an important risk factor for AMD, and angiotensin II (ANG II) is the most important hormone associated with HTN. However, the relevance of ANG II receptors and ANG II effects on RPE have not been investigated yet. Therefore, the expression and regulation of ANG II receptors as well as the ECM turnover were studied in human RPE. ANG II receptors were expressed and upregulated by ANG II in human RPE. This regulation resulted in functional receptor expression, since an increase in intracellular concentration of calcium was observed upon ANG II stimulation. ANG II also increased matrix metalloproteinase (MMP)-2 activity and MMP-14 at the mRNA and protein levels as well as type IV collagen degradation. These ANG II effects were abolished in the presence of the ANG II receptor subtype 1 (AT1) receptor antagonist candesartan. In contrast, ANG II decreased type IV collagen via both AT1 and AT2 receptors, suggesting a synergistic effect of the two receptor subtypes. In conclusion, we have confirmed the presence of ANG II receptors in human RPE and their regulation by ANG II as well as the regulation of ECM molecules via ANG II receptors. Our data support the hypothesis that ANG II may exert biological function in RPE through ANG II receptors and that ANG II may cause dysregulation of molecules that play a major role in the turnover of ECM in RPE basement membrane and Bruch's membrane, suggesting a pathogenic mechanism to explain the link between HTN and AMD. calcium; hypertension; Bruch's membrane EARLY AGE-RELATED MACULAR DEGENERATION (AMD) is one of the most common irreversible causes of severe loss of vision in elderly population (23,39). Dysfunction of retinal photoreceptors is the ultimate cause of vision loss. However, the initial pathogenic target of AMD is the retinal pigment epithelium (RPE) and the subjacent extracellular matrix (Bruch's membrane, or BrM) (25). Although age is the major determinant for developing AMD, clinical studies have revealed a number of systemic and environmental risk factors (23,49,54). Among them, hypertension (HTN) is of special relevance (29,34,37,39). However, the mechanism(s) by which HTN may affect AMD remains unclear. Interestingly, different reports have related that angiotensin II (ANG II), the final product of the renin-angiotensin system (RAS) and the most important hormone associated with HTN, may contribute to chronic diseases (17,43,58,69).Expression and localization ...

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Section: Discussionmentioning

confidence: 98%

Regulation of angiotensin II receptors and extracellular matrix turnover in human retinal pigment epithelium: role of angiotensin II

Striker

Praddaude

Garnica

et al. 2008

American Journal of Physiology-Cell Physiology

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“…This suggests that MAPKs itself may be an intracellular target of oxidative stress in the mouse ES cells that mediates, at least in part, the cell response to H 2 O 2 . Previously, H 2 O 2 was found to induce the release of arachidonic acid (AA) in other cell types, which could be attributed to the activation of p44/42 MAPKs, and the consequent phosphorylation and activation of cytosolic phospholipase A 2 (cPLA 2 ) [45]. These results showed that H 2 O 2 individually stimulated the phosphorylation of p44/42 MAPKs, and the release of AA by mouse ES cells.…”

Section: Discussionmentioning

confidence: 90%

Hydrogen Peroxide Increases [<sup>3</sup>H]-2-Deoxyglucose uptake via MAPKs, cPLA<sub>2</sub>, and NF-κB Signaling Pathways in Mouse Embryonic Stem Cells

Na¹,

Lee²,

Heo³

et al. 2007

Cell Physiol Biochem

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Hydrogen peroxide (H₂O₂) has been shown to act as a signaling molecule that is involved in many cellular functions. This study investigated the effect of H₂O₂ on the [³H]-2-deoxyglucose (2-DG) uptake and its related signaling pathways in mouse embryonic stem (ES) cells. H₂O₂ significantly increased the level of 2-DG uptake in a time- (> 4 hr) and concentration- (>10^-4 M) dependent manner due to an increase in V_max but not K_m. Indeed, H₂O₂ increased the mRNA and protein level of glucose transporter 1 (GLUT 1). PD 98059 (a p44/42 MAPKs inhibitor, 10^-5 M), SB 203580 (a p38 MAPK inhibitor, 10^-6 M), and SP 600125 (a SAPK/JNK inhibitor, 10^-6 M) blocked the H₂O₂-induced increase in 2-DG uptake. H₂O₂ also increased phosphorylation of p44/42 mitogen activated protein kinases (MAPKs), p38 MAPK, and stress-activated protein kinase/Jun-N-terminal kinase (SAPK/JNK). In addition, H₂O₂ stimulated the translocation of cytosolic phospholipase A₂ (cPLA₂) from the cytosolic fraction to the membrane fraction, the release of arachidonic acid, and the activation of NF-κB. AACOCF₃ or mepacrine (cPLA₂ inhibitors, 10^-6 M), SN 50 (NF-κB nucleus translocation inhibitor, 500 ng/ml) or Bay11-7082 (a IκB-α phosphorylation inhibitor, 2x10^-5 M) blocked the H₂O₂-induced increase in 2-DG uptake. H₂O₂ increased the protein level of glucose transporter 1 (GLUT 1), which was blocked by PD 98059, SB 203580, SP 600125, mepacrine, or Bay11-7082. In conclusion, H₂O₂ increases the 2-DG uptake via MAPKs, cPLA₂, and NF-κB signaling pathways in mouse ES cells.

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“…We employed H 2 O 2 to initiate intracellular oxidative stress, as H 2 O 2 is involved in renal disease and is readily permeable to the plasma membrane [28]. A treatment dose of 0.75 m M H 2 O 2 was chosen according to preliminary studies (data not shown) and cell apoptosis was monitored over a period of up to 24 h after H 2 O 2 treatment.…”

Section: Resultsmentioning

confidence: 99%

Suppression of Par-4 Protects Human Renal Proximal Tubule Cells from Apoptosis Induced by Oxidative Stress

Sun

Lu²,

Zhou³

et al. 2010

Nephron Exp Nephrol

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Background: Oxidative stress is an important inducer of cell apoptosis and plays a key role in the development of renal inflammation. The prostate apoptosis response factor-4 (Par-4) gene was originally identified in prostate cells undergoing apoptosis. Subsequently, Par-4 was found to possess potent pro-apoptotic activity in various cellular systems. However, it remains unclear whether Par-4 is involved in oxidant injury of renal tubular epithelial cells. Aims: To determine the role of Par-4 in renal proximal tubular cell apoptosis induced by oxidative stress. Methods: Par-4 gene expression was silenced by small interfering RNA. Renal proximal tubular cells were then exposed to hydrogen peroxide and the effect of Par-4 silencing on apoptosis and expression of phosphorylated Akt and vascular endothelial growth factor was determined. Results: Hydrogen peroxide induced apoptosis and increased Par-4 expression in human renal proximal tubular epithelial cells. Par-4 silencing significantly protected renal proximal tubular cells from apoptosis via activating the PI3K/Akt signaling pathway as Akt phosphorylation was enhanced. Par-4 silencing also ameliorated the downregulation of vascular endothelial growth factor expression induced by oxidative stress. Conclusion: Par-4 gene silencing resulted in PI3K/Akt signaling-dependent inhibition of renal proximal tubular cell apoptosis following oxidative stress.

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Oxidative signaling in renal epithelium: Critical role of cytosolic phospholipase A2 and p38SAPK

Cited by 24 publications

References 45 publications

Regulation of angiotensin II receptors and extracellular matrix turnover in human retinal pigment epithelium: role of angiotensin II

Regulation of angiotensin II receptors and extracellular matrix turnover in human retinal pigment epithelium: role of angiotensin II

Hydrogen Peroxide Increases [<sup>3</sup>H]-2-Deoxyglucose uptake via MAPKs, cPLA<sub>2</sub>, and NF-κB Signaling Pathways in Mouse Embryonic Stem Cells

Suppression of Par-4 Protects Human Renal Proximal Tubule Cells from Apoptosis Induced by Oxidative Stress

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