Expression of Prostaglandin PGE<sub>2</sub>Receptors under Conditions of Aging and Stress and the Protective Effect of the EP2 Agonist Butaprost on Retinal Ischemia

Osborne, Neville N.; Li, Guangyu; Ji, Dan; Costa, Belmira L. Andrade da; Fawcett, Rebecca; Kang, Kui Dong; Rittenhouse, Kay D.

doi:10.1167/iovs.08-3185

Cited by 16 publications

(11 citation statements)

References 59 publications

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“…Here, we show that Sirt1-mediated COX2 induction and PGE 2 production contribute to the protective function of Sirt1 against oxidative stress in RMICs. Protective effects of COX2-derived PGE 2 have been reported in several other studies in multiple organs and tissues such as the liver, kidney, retina, and neurons against injury of diverse causes (35)(36)(37)(38)(39). COX2 has been shown to protect the renal medulla from osmotic stress, and increased COX2 expression is a prerequisite for renal medullary cell survival from hypertonic stress (1,24,25,40).…”

Section: Discussionmentioning

confidence: 68%

Sirt1 activation protects the mouse renal medulla from oxidative injury

He¹,

Wang²,

Zhang³

et al. 2010

J. Clin. Invest.

281

247

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Sirtuin 1 (Sirt1) is a NAD + -dependent deacetylase that exerts many of the pleiotropic effects of oxidative metabolism. Due to local hypoxia and hypertonicity, the renal medulla is subject to extreme oxidative stress. Here, we set out to investigate the role of Sirt1 in the kidney. Our initial analysis indicated that it was abundantly expressed in mouse renal medullary interstitial cells in vivo. Knocking down Sirt1 expression in primary mouse renal medullary interstitial cells substantially reduced cellular resistance to oxidative stress, while pharmacologic Sirt1 activation using either resveratrol or SRT2183 improved cell survival in response to oxidative stress. The unilateral ureteral obstruction (UUO) model of kidney injury induced markedly more renal apoptosis and fibrosis in Sirt1 +/-mice than in wild-type controls, while pharmacologic Sirt1 activation substantially attenuated apoptosis and fibrosis in wild-type mice. Moreover, Sirt1 deficiency attenuated oxidative stress-induced COX2 expression in cultured mouse renal medullary interstitial cells, and Sirt1 +/-mice displayed reduced UUO-induced COX2 expression in vivo. Conversely, Sirt1 activation increased renal medullary interstitial cell COX2 expression both in vitro and in vivo. Furthermore, exogenous PGE 2 markedly reduced apoptosis in Sirt1-deficient renal medullary interstitial cells following oxidative stress. Taken together, these results identify Sirt1 as an important protective factor for mouse renal medullary interstitial cells following oxidative stress and suggest that the protective function of Sirt1 is partly attributable to its regulation of COX2 induction. We therefore suggest that Sirt1 provides a potential therapeutic target to minimize renal medullary cell damage following oxidative stress.

show abstract

Section: Discussionmentioning

confidence: 68%

Sirt1 activation protects the mouse renal medulla from oxidative injury

He¹,

Wang²,

Zhang³

et al. 2010

J. Clin. Invest.

281

247

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show abstract

“…Expression of EP1 (38 kDa), EP2 (52 kDa), EP3 (53-98 kDa), or EP4 (53 kDa) receptor in the rat RVLM and PC12 cells. JWF2 cells or kidney homogenates were used as positive controls; the wide range in molecular weight in EP3 receptor expression is ascribed to the different forms of the receptor (Osborne et al, 2009) and is verified using blots of rat RVLM, PC12 cells, or kidney when EP3 receptor primary antibody was preincubated with its blocking peptide. Quantification of blots from RVLM or PC12 cells is presented in the upper panel.…”

Section: Methodsmentioning

confidence: 99%

“…Notably, the molecular weight of the EP3 receptor varies from 53 to 98 kDa (Fig. 1) according to the degree of its post-translational modification, and the average of all bands was used to determine its expression level, as reported (Osborne et al, 2009).…”

Section: Ep Receptor Expression In the Rvlm And Pc12mentioning

confidence: 99%

Rostral Ventrolateral Medulla EP3 Receptor Mediates the Sympathoexcitatory and Pressor Effects of Prostaglandin E₂ in Conscious Rats

Rezq

Abdel‐Rahman

2016

J Pharmacol Exp Ther

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Whereas few studies have dealt with the central sympathoexcitatory action of the inflammatory prostanoid prostaglandin E 2 (PGE 2 ), there is no information on the expression and cardiovascular function of different PGE 2 (EP) receptors in one of the major cardiovascular-regulating nuclei, the rostral ventrolateral medulla (RVLM). The current study aimed at filling this knowledge gap as well as elucidating the implicated molecular mechanisms. To achieve these goals, we showed the expression of EP2, EP3, and EP4 receptors in the RVLM and investigated their cardiovascular roles in conscious rats, ex vivo as well as in cultured PC12 cells. Intra-RVLM PGE 2 significantly increased blood pressure and sympathetic dominance (spectral analysis). Studies with selective EP receptor subtype agonists and antagonists showed that these PGE 2 -evoked responses were only replicated by intra-RVLM activation of the EP3 receptor with its agonist sulprostone. The RVLM of PGE 2 -treated rats exhibited increases in c-Fos expression and extracellular signal-regulated kinase 1/2 and neuronal nitric oxide synthase phosphorylation along with oxidative stress, and PGE 2 increased L-glutamate release in PC12 cells (surrogates of RVLM neurons). Abrogation of the PGE 2 -evoked pressor and biochemical responses only occurred following EP3 receptor blockade (N-[(5-Bromo-2-methoxyphenyl)sulfonyl]-3-[2-(2-naphthalenylmethyl) phenyl]-2-propenamide, L-798106). These findings suggest the dependence of RVLM PGE 2 -mediated sympathoexcitation/ pressor response on local EP3 receptor signaling in conscious rats, and highlight central EP3 receptor blockade as a potential therapeutic modality for hypertension management.

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“…Experiments have been largely designed to assess vision-sparing potential in glaucoma and retinal disease (Andrade da Mori et al, 2009;Osborne et al, 2009). The underlying EP 2 -regulated signaling mechanisms involved in ocular neuroprotection have received little attention but are probably likely similar to those reported for CNS neurons.…”

Section: Distribution and Biological Functionsmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress

Woodward

Jones

Narumiya³

2011

Pharmacol Rev

391

414

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Expression of Prostaglandin PGE₂Receptors under Conditions of Aging and Stress and the Protective Effect of the EP2 Agonist Butaprost on Retinal Ischemia

Cited by 16 publications

References 59 publications

Sirt1 activation protects the mouse renal medulla from oxidative injury

Sirt1 activation protects the mouse renal medulla from oxidative injury

Rostral Ventrolateral Medulla EP3 Receptor Mediates the Sympathoexcitatory and Pressor Effects of Prostaglandin E₂ in Conscious Rats

International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress

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Expression of Prostaglandin PGE2Receptors under Conditions of Aging and Stress and the Protective Effect of the EP2 Agonist Butaprost on Retinal Ischemia

Cited by 16 publications

References 59 publications

Sirt1 activation protects the mouse renal medulla from oxidative injury

Sirt1 activation protects the mouse renal medulla from oxidative injury

Rostral Ventrolateral Medulla EP3 Receptor Mediates the Sympathoexcitatory and Pressor Effects of Prostaglandin E2 in Conscious Rats

International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress

Contact Info

Product

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Expression of Prostaglandin PGE₂Receptors under Conditions of Aging and Stress and the Protective Effect of the EP2 Agonist Butaprost on Retinal Ischemia

Rostral Ventrolateral Medulla EP3 Receptor Mediates the Sympathoexcitatory and Pressor Effects of Prostaglandin E₂ in Conscious Rats