Multiple death pathways in retina-derived 661W cells following growth factor deprivation: crosstalk between caspases and calpains.
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 long-term 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.
Gómez-Vicente
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V
Cell Development and Disease Laboratory, Department of Biochemistry, Biosciences Research Institute, University College Cork, Cork, Ireland.
Donovan
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M
Cotter
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TG
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002154:Calpain / Q000037:antagonists & inhibitors / Q000378:metabolism*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006133:Growth Substances / Q000172:deficiency* / Q000378:metabolism; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D017949:Retinal Cone Photoreceptor Cells / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*
D061945:Caspase Inhibitors; D016895:Culture Media, Serum-Free; D006133:Growth Substances; C116500:acetyl-leucinal-nor-leucinal; D002154:Calpain; D020169:Caspases; C449000:m-calpain; D007930:Leucine