Oxidative stress induces caspase-independent retinal apoptosis in vitro

Carmody, Ruaidhrı́ J.; Cotter, Thomas G.

doi:10.1038/sj.cdd.4400646

Cited by 122 publications

(84 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…30,41 They represent an invaluable tool for the study of cone PCD, given the detection problems that can arise in studying dynamic events in cells that account for a mere 2.8% of total photoreceptors in the mouse retina. 28 In spite of the fact that previous studies in our group ruled out the involvement of caspases in several in vitro and in vivo models of photoreceptor degeneration, [42][43][44] (data not shown) and -12 were active during apoptosis of 661W cells. This conflicting data can readily be explained if one considers the differences between the models employed.…”

Section: Discussionmentioning

confidence: 57%

Multiple death pathways in retina-derived 661W cells following growth factor deprivation: crosstalk between caspases and calpains

2005

Self Cite

View full text Add to dashboard Cite

During development of the mammalian retina, neurons that do not succeed in establishing functional synaptic connections are eliminated by apoptosis, allowing the formation of a finely tuned network. Growth factors play a crucial role in controlling the balance between apoptosis and survival signals not only at developmental stages but also in longterm preservation of retinal functions. In the present work, we explore the apoptotic mechanisms triggered by growth factor deprivation of retina-derived 661W cells. Under serum starvation conditions, these cone photoreceptors underwent cell death with participation of caspase-9, -3 and -12. Interestingly, inhibition of caspases did not prevent apoptosis but only resulted in a temporary delay. We show m-calpain activation in parallel with caspases, indicating that more than one execution pathway is available to cone photoreceptors. Moreover, crosstalk of the caspase and calpain pathways was detected, suggesting a loop that may act to amplify the apoptotic cascade.

show abstract

Section: Discussionmentioning

confidence: 57%

Multiple death pathways in retina-derived 661W cells following growth factor deprivation: crosstalk between caspases and calpains

2005

Self Cite

View full text Add to dashboard Cite

show abstract

“…Caspase-independent apoptosis has also been observed in neuronal cells in response to ␤-amyloid, nitric oxide, and traumatic brain injury (Okuno et al, 1998;Selznick et al, 2000;Zhang et al, 2002) and in the models of photoreceptor cell death both in vivo (Carmody and Cotter, 2000) and in vitro (Donovan and Cotter, 2002). Previous studies showed that TMS increases DNA cleavage by S1 nuclease at both loop regions in an asymmetric way in G-quadruplex structures (Kim et al, 2003), and we found that TMS induces a rapid activation of PARP-1 and ␥H2AX, consistent with a DNA damage response.…”

Section: Discussionmentioning

confidence: 99%

Telomere Protection Mechanisms Change during Neurogenesis and Neuronal Maturation: Newly Generated Neurons Are Hypersensitive to Telomere and DNA Damage

Cheng¹,

Shin‐ya²,

Wan³

et al. 2007

J. Neurosci.

View full text Add to dashboard Cite

Telomeres are DNA-protein complexes at the ends of eukaryotic chromosomes that play an important role in maintaining the integrity of the genome. In proliferative stem cells and cancer cells, telomere length is maintained by telomerase, and telomere structure and functions are regulated by telomere-associated proteins. We find that telomerase levels are high in embryonic cortical neural progenitor cells (NPCs) and low in newly generated neurons (NGNs) and mature neurons (MNs). In contrast, telomere repeat-binding factor 2 (TRF2) expression is undetectable in early brain development in vivo and in cultured NPCs and is expressed at progressively higher levels as NPCs cease proliferation and differentiate into postmitotic neurons. The telomere-disrupting agent telomestatin induces a DNA damage response and apoptosis in NGNs (which have low levels of TRF2 and telomerase), whereas NPCs (which have high levels of telomerase) and MNs (which have high levels of TRF2) are resistant to telomere damage. Overexpression of TRF2 in NGNs protects them against death induced by telomestatin and other DNA-damaging agents. Knockdown of TRF2 expression in MNs and knock-out of telomerase reverse transcriptase in NPCs increased their sensitivity to telomere-and DNA-damaging agents but did not affect the vulnerability of NGNs. These findings suggest that TRF2 and telomerase function as distinct telomere protection mechanisms during the processes of neurogenesis and neuronal maturation and that hypersensitivity of NGNs to telomere damage results from relative deficiencies of both telomerase and TRF2.

show abstract

“…The presence of exogenous GSH has a similar effect to CsA and verapamil. Previous studies (56,57) have shown that PS translocation is independent of both nuclear activity (55) and caspase activation. It seems most likely that in HaCaT cells GSH efflux is involved in membrane rearrangement rather than caspase activation or DNA fragmentation in UVA-induced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Role of Reduced Glutathione Efflux in Apoptosis of Immortalized Human Keratinocytes Induced by UVA

Huang

Ramirez

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

We have investigated the role played by GSH efflux in apoptosis of human HaCaT keratinocytes induced by UVA irradiation. UVA irradiation of HaCaT cells caused a rapid rise in GSH efflux across the intact cell membrane, followed by an increase in apoptosis. GSH efflux was stimulated by glucose and was reduced by the addition of exogenous GSH and intracellular GSH depletion by buthionine sulfoximine, suggesting that GSH transport is active and is influenced by the GSH concentration gradient across the cell membrane. Verapamil and cyclosporin A, blockers of the multidrug resistanceassociated protein, decreased UVA-induced GSH efflux. GSH efflux occurred within 2 h of UVA irradiation, suggesting that the stimulation of GSH efflux is due to an increase in the activity of pre-existing multidrug resistance-associated protein transporter carrier. Although inhibition of GSH efflux did not affect caspase activation and DNA fragmentation, it delayed the gradual increase in plasma membrane permeability and reduced phosphatidylserine translocation in HaCaT cells. It is therefore likely that upon UVA irradiation, GSH efflux increased the intracellular oxidative stress without intervention of reactive oxygen species, thus resulting in more phosphatidylserine externalization and membrane rearrangement. These provide targets for macrophage recognition and phagocytosis and thus minimize the potential to invoke inflammation or neoplastic transformation.

show abstract

Oxidative stress induces caspase-independent retinal apoptosis in vitro

Cited by 122 publications

References 63 publications

Multiple death pathways in retina-derived 661W cells following growth factor deprivation: crosstalk between caspases and calpains

Multiple death pathways in retina-derived 661W cells following growth factor deprivation: crosstalk between caspases and calpains

Telomere Protection Mechanisms Change during Neurogenesis and Neuronal Maturation: Newly Generated Neurons Are Hypersensitive to Telomere and DNA Damage

Role of Reduced Glutathione Efflux in Apoptosis of Immortalized Human Keratinocytes Induced by UVA

Contact Info

Product

Resources

About