Neuroactive steroids protect retinal pigment epithelium against oxidative stress

Bucolo, Claudio; Drago, Filippo; Lin, Lishan; Reddy, Venkat N.

doi:10.1097/00001756-200508010-00014

Cited by 21 publications

(12 citation statements)

References 18 publications

(18 reference statements)

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“…In ARPE-19 cells, other time points and other toxicity measures have been used [9–16,35,46–48]. Although H 2 O 2 concentration changes dynamically over time especially after pulse addition, outcomes are typically determined at a fixed post-treatment interval.…”

Section: Resultsmentioning

confidence: 99%

Dynamics of H2O2 availability to ARPE-19 cultures in models of oxidative stress

Kaczara

Sarna

Burke

2010

Free Radical Biology and Medicine

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Oxidative injury to cells such as the retinal pigment epithelium (RPE) is often modeled using H 2 O 2 -treated cultures, but H 2 O 2 concentrations are not sustained in culture medium. Here medium levels of H 2 O 2 and cytotoxicity were analyzed in ARPE-19 cultures following H 2 O 2 delivery as a single pulse or with continuous generation using glucose oxidase (GOx). When added as a pulse, H 2 O 2 is rapidly depleted (within 2 hr); cytotoxicity at 24, determined by the MTT assay for mitochondrial function, is unaffected by medium replacement at 2 hr. Continuous generation of H 2 O 2 produces complex outcomes. At low GOx concentrations, H 2 O 2 levels are sustained by conditions in which generation matches depletion, but when GOx concentrations produce cytotoxic levels of H 2 O 2 , oxidant depletion accelerates. Acceleration results partly from the release of contents from oxidant damaged cells as indicated by testing depletion after controlled membrane disruption with detergents. Cytotoxicity analyses show that cells can tolerate short exposure to high H 2 O 2 doses delivered as a pulse but are susceptible to lower chronic doses. The results provide broadly applicable guidance for using GOx to produce sustained H 2 O 2 levels in cultured cells. This approach will be specifically useful for modeling chronic stress relevant for RPE aging and have wider value for studying cellular effects of sub-lethal oxidant injury and for evaluating antioxidants that may protect significantly against mild but not lethal stress.

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Section: Resultsmentioning

confidence: 99%

Dynamics of H2O2 availability to ARPE-19 cultures in models of oxidative stress

Kaczara

Sarna

Burke

2010

Free Radical Biology and Medicine

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“…Since the physiological function of RPE cells is responsible for clearance of oxidants derived from photoreceptor turnover, ARPE-19 cells have been used to explore oxidant-mediated insults and related protective factors in a number of recent studies. Hepatocyte growth factor (HGF), pigment epithelium-derived factor, keratinocyte growth factor, sigma receptor ligands and neuroactive steroids have been shown to prevent oxidantinduced apoptosis in ARPE-19 cells [7,29,[37][38][39]. In these studies, pretreatment with HGF abrogated oxidant-mediated AIF translocation; however, the underlying mechanism has not been elucidated [7].…”

Section: Discussionmentioning

confidence: 99%

Activation of mitogen-activated protein kinases is essential for hydrogen peroxide -induced apoptosis in retinal pigment epithelial cells

Yang

Cheng

et al. 2006

Apoptosis

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Retinal pigment epithelial (RPE) cells are constantly exposed to oxidative injury while clearing byproducts of photoreceptor turnover, a circumstance thought to be responsible for degenerative retinal diseases. The mechanisms of hydrogen peroxide (H(2)O(2))-induced apoptosis in RPE cells are not fully understood. We studied signal transduction mechanisms of H(2)O(2)-induced apoptosis in the human RPE cell line ARPE-19. Activation of two stress kinases (JNK and p38) occurs during H(2)O(2) stimulation, and H(2)O(2)-mediated cell death was significantly reduced by their specific inhibition. Exposure to a lethal dose of H(2)O(2) elicited Bax translocation to the mitochondria and release of apoptosis-inducing factor (AIF) from the mitochondria, both of which were abolished by either JNK- or p38-specific inhibitors. Both H(2)O(2)-induced cell death and JNK/p38 phosphorylation were partially inhibited by C. difficile toxin B, inhibitor of Rho, Rac, and cdc42. Use of pull-down assays revealed that the small GTPase activated by H(2)O(2) is Rac1. This study is the first to demonstrate that H(2)O(2) induces a Rac1/JNK1/p38 signaling cascade, and that JNK and p38 activation is important for H(2)O(2)-induced apoptosis as well as AIF/Bax translocation of RPE cells.

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“…24 NS are also involved in the antioxidant defense mechanisms of the nervous system. 25,26 The results of an earlier study has shown that PROG inhibits the lipid peroxidation as evidenced by the reduced levels of 8-isoprostaglandin F2 alpha in brains of PROGtreated rats in a cerebral contusion model. 27 In another study, DHEA pretreatment was found to reduce DNA damage induced by oxidative insult.…”

Section: Introductionmentioning

confidence: 99%

Effect of progesterone on phosphamidon-induced impairment of memory and oxidative stress in rats

et al. 2011

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Progesterone (a neurosteroid) is an important modulator of the nervous system functioning. Organophosphorus pesticides like phosphamidon have been shown to adversely affect memory and induce oxidative stress on both acute and chronic exposure. The present study was therefore designed to investigate the effects of progesterone (PROG) on phosphamidon-induced modulation of cognitive function and oxidative stress in rats. Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus and transfer latency (TL) on an elevated plus maze. Oxidative stress was assessed by examining the levels of thiobarbituric acid reactive species (TBARS) and non-protein thiols (NP-SH) in isolated homogenized whole brain samples. The results showed a significant reduction in SDL and prolongation of TL in the phosphamidon (1.74 mg/kg/d; p.o.) treated group at weeks 6 and 8 as compared to the control group. Two weeks treatment with PROG (15 mg/kg/d; i.p.) antagonized the effect of phosphamidon on SDL as well as TL. Phosphamidon alone produced a significant increase in the brain TBARS levels and decrease in the brain NP-SH levels. Treatment with PROG (15 mg/kg/d; i.p.) attenuated the effect of phosphamidon on oxidative stress. Together, the results showed that progesterone attenuated the cognitive dysfunction and increased oxidative stress induced by phosphamidon in the brain.

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Neuroactive steroids protect retinal pigment epithelium against oxidative stress

Cited by 21 publications

References 18 publications

Dynamics of H2O2 availability to ARPE-19 cultures in models of oxidative stress

Dynamics of H2O2 availability to ARPE-19 cultures in models of oxidative stress

Activation of mitogen-activated protein kinases is essential for hydrogen peroxide -induced apoptosis in retinal pigment epithelial cells

Effect of progesterone on phosphamidon-induced impairment of memory and oxidative stress in rats

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