Synthesis of Sphingosine Is Essential for Oxidative Stress-Induced Apoptosis of Photoreceptors

Abrahan, Carolina E.; Miranda, Gisela Edit; Agnolazza, Daniela L.; Politi, Luis E.; Rotstein, Nora P.

doi:10.1167/iovs.09-3909

Cited by 47 publications

(52 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Exogenous addition of Sph leads to photoreceptor apoptosis and inhibiting Sph metabolization to Cer does not prevent this death ( 191 ), implying Sph is by itself a mediator of apoptosis. Exogenous Sph induces mitochondrial depolarization, cytochrome C release, and production of reactive oxygen species in photoreceptors, whereas inhibiting Sph synthesis preserves mitochondrial membrane integrity ( 191 ). These results are consistent with the involvement of the mitochondrial pathway in Sph-induced apoptosis in several cell types; mitochondria are among the major cellular sources of reactive oxygen species, and both Sph and Cer have been shown to increase their generation ( 196 ).…”

Section: Sphingosine In the Retinamentioning

confidence: 99%

“…4 ). Noteworthy, this DHA protection is blocked when SphK1 activity is inhibited ( 191 ), implying that a decrease in Sph levels through its phosphorylation to S1P is required for DHA protective effect. Hence, we propose that increased oxidative stress in different pathological conditions might promote the synthesis of Cer in photoreceptors, which is then at least partially metabolized to Sph.…”

Section: Ceramide In the Retinamentioning

confidence: 99%

“…Recent data from our laboratory demonstrates that Sph acts as a mediator of photoreceptor apoptosis, together with Cer, in retina neurons in culture ( Fig. 4 ) ( 191 ). Oxidative stress rapidly increases [ 3 H]Sph levels in cultured photoreceptors, whereas inhibiting Sph synthesis with an alkaline ceramidase inhibitor prevents the apoptosis of photoreceptors induced by Cer or by oxidative stress ( 191 ).…”

Section: Sphingosine In the Retinamentioning

confidence: 99%

“…4 ) ( 191 ). Oxidative stress rapidly increases [ 3 H]Sph levels in cultured photoreceptors, whereas inhibiting Sph synthesis with an alkaline ceramidase inhibitor prevents the apoptosis of photoreceptors induced by Cer or by oxidative stress ( 191 ). The easy interconversion between Cer and Sph has made it complex to distinguish their individual roles and effects.…”

Section: Sphingosine In the Retinamentioning

confidence: 99%

“…Though Sph may be converted back to Cer to induce apoptosis, inhibiting this conversion does not prevent apoptosis in several cell lines ( 49,192,193 ); conversely, blocking Sph synthesis attenuates apoptosis due to different death stimuli ( 194,195 ). Exogenous addition of Sph leads to photoreceptor apoptosis and inhibiting Sph metabolization to Cer does not prevent this death ( 191 ), implying Sph is by itself a mediator of apoptosis. Exogenous Sph induces mitochondrial depolarization, cytochrome C release, and production of reactive oxygen species in photoreceptors, whereas inhibiting Sph synthesis preserves mitochondrial membrane integrity ( 191 ).…”

Section: Sphingosine In the Retinamentioning

confidence: 99%

See 4 more Smart Citations

Regulating survival and development in the retina: key roles for simple sphingolipids

Rotstein

Miranda

Abrahan

et al. 2010

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

tions as structural membrane components and energetic fuels. However, the fi ndings of the previous half century have extended these roles, shedding light on their indisputable relevance as signaling molecules controlling key aspects of cellular life and development. The identifi cation of diacylglycerol and inositol 1,4,5 triphosphate ( 1 ) as second messengers seemed at the time a peculiarity of these lipids. The subsequent fi ndings of the roles of arachidonic acid metabolites ( 2 ), platelet activating factor ( 3 ), and other minor inositol lipids ( 4 ) in cell signaling began to establish that being intracellular messengers was not an oddity but a habitual task for lipids in cells. The family of lipid signaling molecules largely expanded in the last two decades, when several sphingolipids were successively shown to regulate a multiplicity of cell functions. Sphingosine (Sph) was the fi rst sphingolipid to be established as a bioactive lipid, involved in the regulation of protein kinase (PK)C activity ( 5 ). Ceramide (Cer) and sphingosine-1-phosphate (S1P) were next shown to signal a myriad of cell functions and the number of sphingolipid molecules with bioactive properties has gone on enlarging in recent years ( 6, 7 ).Though a vast literature exists on the functions of sphingolipids in several tissues, less is known concerning its roles in the eye, and in the retina in particular. Accumulation of sphingolipids originated in defects in the lysosomal Abstract Many sphingolipids have key functions in the regulation of crucial cellular processes. Ceramide (Cer) and sphingosine (Sph) induce growth arrest and cell death in multiple situations of cellular stress. On the contrary, sphingosine-1-phosphate (S1P), the product of Sph phosphorylation, promotes proliferation, differentiation, and survival in different cell systems. This review summarizes the roles of these simple sphingolipids in different tissues and then analyzes their possible functions in the retina. Alterations in proliferation, neovascularization, differentiation, and cell death are critical in major retina diseases and collective evidence points to a role for sphingolipids in these processes. Cer induces infl ammation and apoptosis in endothelial and retinal pigmented epithelium cells, leading to several retinopathies. S1P can prevent this death but also promotes cell proliferation that might lead to neovascularization and fibrosis. Recent data support Cer and Sph as crucial mediators in the induction of photoreceptor apoptosis in diverse models of oxidative damage and neurodegeneration, and suggest that regulating their metabolism can prevent this death. New evidence proposes a central role for S1P controlling photoreceptor survival and differentiation. Finally, this review discusses the ability of trophic factors to regulate sphingolipid metabolism and transactivate S1P signaling pathways to control survival and development in retina photoreceptors. When asked about the roles of cellular lipids, the fi rst thought usually coming to our minds re...

show abstract

Section: Sphingosine In the Retinamentioning

confidence: 99%

Section: Ceramide In the Retinamentioning

confidence: 99%

Section: Sphingosine In the Retinamentioning

confidence: 99%

Section: Sphingosine In the Retinamentioning

confidence: 99%

Section: Sphingosine In the Retinamentioning

confidence: 99%

See 3 more Smart Citations

Regulating survival and development in the retina: key roles for simple sphingolipids

Rotstein

Miranda

Abrahan

et al. 2010

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

show abstract

A Near‐Infrared Fluorogenic Probe for Rapid, Specific, and Ultrasensitive Detection of Sphingosine in Living Cells and In Vivo

Chen,

Hao,

Wang

et al. 2023

Advanced Science

View full text Add to dashboard Cite

Sphingosine (Sph) plays important roles in various complex biological processes. Abnormalities in Sph metabolism can result in various diseases, including neurodegenerative disorders. However, due to the lack of rapid and accurate detection methods, understanding sph metabolic in related diseases is limited. Herein, a series of near‐infrared fluorogenic probes DMS‐X (X = 2F, F, Cl, Br, and I) are designed and synthesized. The fast oxazolidinone ring formation enables the DMS‐2F to detect Sph selectively and ultrasensitively, and the detection limit reaches 9.33 ± 0.41 nm. Moreover, it is demonstrated that DMS‐2F exhibited a dose‐ and time‐dependent response to Sph and can detect sph in living cells. Importantly, for the first time, the changes in Sph levels induced by Aβ42 oligomers and H2O2 are assessed through a fluorescent imaging approach, and further validated the physiological processes by which Aβ42 oligomers and reactive oxygen species (ROS)‐induce changes in intracellular Sph levels. Additionally, the distribution of Sph in living zebrafish is successfully mapped by in vivo imaging of a zebrafish model. This work provides a simple and efficient method for probing Sph in living cells and in vivo, which will facilitate investigation into the metabolic process of Sph and the connection between Sph and disease pathologies.

show abstract

Effect ofin vitrodigested cod liver oil of different quality on oxidative, proteomic and inflammatory responses in the yeastSaccharomyces cerevisiaeand human monocyte-derived dendritic cells

Larsson

Istenič

Wulff

et al. 2015

J. Sci. Food Agric.

View full text Add to dashboard Cite

show abstract

Synthesis of Sphingosine Is Essential for Oxidative Stress-Induced Apoptosis of Photoreceptors

Cited by 47 publications

References 61 publications

Regulating survival and development in the retina: key roles for simple sphingolipids

Regulating survival and development in the retina: key roles for simple sphingolipids

A Near‐Infrared Fluorogenic Probe for Rapid, Specific, and Ultrasensitive Detection of Sphingosine in Living Cells and In Vivo

Effect ofin vitrodigested cod liver oil of different quality on oxidative, proteomic and inflammatory responses in the yeastSaccharomyces cerevisiaeand human monocyte-derived dendritic cells

Contact Info

Product

Resources

About