Necrostatin-1 Protects Photoreceptors from Cell Death and Improves Functional Outcome after Experimental Retinal Detachment

Dong, Kai; Zhu, Hong; Gong, Yuanyuan; Wang, Fenghua; Wang, Wenqiu; Zheng, Zhi; Zhang, Yu; Gu, Qing; Xu, Xun; Sun, Xiaodong

doi:10.1016/j.ajpath.2012.07.029

Cited by 62 publications

(31 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since Bax can be activated during necrosis (Cabon et al, 2012), we examined the involvement of necrosis using a pharmacological approach to further understand retinal cell death by mediated by atRAL. ARPE-19 cells and WT cultured mouse neural retinas were pre-treated with Necrostatin-1 (Nec-1), which is commonly used as an inhibitor of necrosis (Dong et al, 2012; Trichonas et al, 2010), and protective effects Nec-1 on atRAL cell toxicity was evaluated. Notably, no apparent protective effects of Nec-1 were observed, whereas BIP treatment prevented ARPE-19 cells from atRAL-induced death in a dose-dependent manner (Fig.…”

Section: Resultsmentioning

confidence: 99%

All-trans-retinal induces Bax activation via DNA damage to mediate retinal cell apoptosis

Sawada

Perusek

Kohno

et al. 2014

Experimental Eye Research

View full text Add to dashboard Cite

The current study investigates the cellular events which trigger activation of proapoptotic Bcl-2-associated X protein (Bax) in retinal cell death induced by all-trans-retinal (atRAL). Cellular events which activate Bax, such as DNA damage by oxidative stress and phosphorylation of p53, were evaluated by immunochemical and biochemical methods using ARPE-19 cells, 661W cells, cultured neural retinas and a retinal degeneration model, Abca4−/−Rdh8−/− mice. atRAL-induced Bax activation in cultured neural retinas was examined by pharmacological and genetic methods. Other Bax-related cellular events were also evaluated by pharmacological and biochemical methods. Production of 8-OHdG, a DNA damage indicator, and the phosphorylation of p53 at Ser 46 were detected prior to Bax activation in ARPE-19 cells incubated with atRAL. Light exposure to Abca4−/−Rdh8−/− mice also caused the above mentioned events in conditions of short term intense light exposure and regular room lighting conditions. Incubation with Bax inhibiting peptide and deletion of the Bax gene partially protected retinal cells from atRAL toxicity in cultured neural retina. Necrosis was demonstrated not to be the main pathway in atRAL mediated cell death. Bcl-2-interacting mediator and Bcl-2 expression levels were not altered by atRAL in vitro. atRAL-induced oxidative stress results in DNA damage leading to the activation of Bax by phosphorylated p53. This cascade is closely associated with an apoptotic cell death mechanism rather than necrosis.

show abstract

Section: Resultsmentioning

confidence: 99%

All-trans-retinal induces Bax activation via DNA damage to mediate retinal cell apoptosis

Sawada

Perusek

Kohno

et al. 2014

Experimental Eye Research

View full text Add to dashboard Cite

show abstract

“…169 Concomitantly, another group reported that zVAD-fmk not only failed to prevent photoreceptor death upon retinal detachment but also led to increased necrotic cell death, which could be ameliorated by Nec-1 administration or a RIPK3-deficient background. Indeed, necrotic cell death is a hallmark of retinal detachment.…”

Section: Ophthalmology and Necroptosismentioning

confidence: 97%

The in vivo evidence for regulated necrosis

Tonnus

Linkermann

2017

Immunological Reviews

103

View full text Add to dashboard Cite

Necrosis is a hallmark of several widespread diseases or their direct complications. In the past decade, we learned that necrosis can be a regulated process that is potentially druggable. RIPK3- and MLKL-mediated necroptosis represents by far the best studied pathway of regulated necrosis. During necroptosis, the release of damage-associated molecular patterns (DAMPs) drives a phenomenon referred to as necroinflammation, a common consequence of necrosis. However, most studies of regulated necrosis investigated cell lines in vitro in a cell autonomous manner, which represents a non-physiological situation. Conclusions based on such work might not necessarily be transferrable to disease states in which synchronized, non-cell autonomous effects occur. Here, we summarize the current knowledge of the pathophysiological relevance of necroptosis in vivo, and in light of this understanding, we reassess the morphological classification of necrosis that is generally used by pathologists. Along these lines, we discuss the paucity of data implicating necroptosis in human disease. Finally, the in vivo relevance of non-necroptotic forms of necrosis, such as ferroptosis, is addressed.

show abstract

“…Recently, an independent group has also detected the involvement of RIP kinase in photoreceptor cell loss after RD in a non-pigmented strain of rats. (Dong et al, 2012). …”

Section: Rip Kinase and Necrosismentioning

confidence: 99%

Photoreceptor cell death and rescue in retinal detachment and degenerations

Murakami

Notomi

Hisatomi

et al. 2013

Progress in Retinal and Eye Research

190

181

View full text Add to dashboard Cite

Photoreceptor cell death is the ultimate cause of vision loss in various retinal disorders, including retinal detachment (RD). Photoreceptor cell death has been thought to occur mainly through apoptosis, which is the most characterized form of programmed cell death. The caspase family of cysteine proteases plays a central role for inducing apoptosis, and in experimental models of RD, dying photoreceptor cells exhibit caspase activation; however, there is a paradox that caspase inhibition alone does not provide a sufficient protection against photoreceptor cell loss, suggesting that other mechanisms of cell death are involved. Recent accumulating evidence demonstrates that non-apoptotic forms of cell death, such as autophagy and necrosis, are also regulated by specific molecular machinery, such as those mediated by autophagy-related proteins and receptor-interacting protein kinases, respectively. Here we summarize the current knowledge of cell death signaling and its roles in photoreceptor cell death after RD and other retinal degenerative diseases. A body of studies indicate that not only apoptotic but also autophagic and necrotic signaling are involved in photoreceptor cell death, and that combined targeting of these pathways may be an effective neuroprotective strategy for retinal diseases associated with photoreceptor cell loss.

show abstract

Necrostatin-1 Protects Photoreceptors from Cell Death and Improves Functional Outcome after Experimental Retinal Detachment

Cited by 62 publications

References 41 publications

All-trans-retinal induces Bax activation via DNA damage to mediate retinal cell apoptosis

All-trans-retinal induces Bax activation via DNA damage to mediate retinal cell apoptosis

The in vivo evidence for regulated necrosis

Photoreceptor cell death and rescue in retinal detachment and degenerations

Contact Info

Product

Resources

About