RT Journal Article
SR Electronic
T1 <em>c-fos</em> Controls the “Private Pathway” of Light-Induced Apoptosis of Retinal Photoreceptors
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 81
OP 88
DO 10.1523/JNEUROSCI.20-01-00081.2000
VO 20
IS 1
A1 Andreas Wenzel
A1 Christian Grimm
A1 Andreas Marti
A1 Nicole Kueng-Hitz
A1 Farhad Hafezi
A1 Günter Niemeyer
A1 Charlotte E. Remé
YR 2000
UL http://www.jneurosci.org/content/20/1/81.abstract
AB White light (5 klux for 2 hr) induces apoptosis of rod photoreceptors in wild-type mice (c-fos+/+) within 24 hr, whereas rods of c-fos knock-out mice (c-fos−/−) are protected (Hafezi et al., 1997b).The range of this protection was tested by analyzing retinas ofc-fos+/+ andc-fos−/− mice up to 10 d after exposure to threefold increased light intensities (15 klux for 2 hr). In c-fos−/− mice, rods were unaffected, whereas they were destroyed inc-fos+/+ mice. After light exposure, mitochondrial damage in rods was observed exclusively inc-fos+/+ mice. Electroretinograms recorded 48 hr after exposure revealed a decrease of all components inc-fos+/+ mice but indicated no light-induced loss of function inc-fos−/− mice. Thus, inc-fos−/− mice, light-induced apoptosis is blocked or its threshold is elevated more than threefold.Increased activity of the transcription factor activator protein-1 (AP-1) in retinas of light-exposedc-fos+/+ mice indicated an acute contribution of AP-1 to apoptosis induction. AP-1 activity increased already during exposure and peaked ∼6 hr thereafter, coinciding with the appearance of major morphological signs of apoptosis. Activated AP-1 mainly consisted of c-Fos/Jun heterodimers. Inc-fos−/− mice, AP-1 activity remained unchanged, indicating that no other Jun- or Fos-family member could substitute for c-Fos. Like damaging light,N-methyl-N-nitrosourea (MNU) induced AP-1 containing c-Fos in c-fos+/+ mice and did not induce AP-1 in c-fos−/−mice. In contrast to light, however, MNU induced apoptosis in rods ofc-fos−/− mice. Thus, c-Fos is essential for a specific premitochondrial “private apoptotic pathway” induced by light but not for the execution of apoptosis induced by other stimuli.