TY - JOUR
T1 - Characterization of cell death pathways in murine retinal neurodegeneration implicates cytochrome c release, caspase activation, and bid cleavage
AU - Jomary, C
AU - Neal, M J
AU - Jones, S E
PY - 2001
Y1 - 2001
N2 - Apoptosis is considered to be the final common pathway of photoreceptor cell death in different inherited retinal diseases. However, apoptosis encompasses diverse pathways of molecular interactions culminating in cellular demise. To begin dissecting these interactions, we have investigated key participants in the rd (retinal degeneration) model of retinal neurodegeneration. By Western blot analysis and immunocytochemistry, we found that cytochrome c release occurs in rd retinas concurrently with the activation of the proapoptotic protein Bid. Active forms of caspase-8 and the mitogen-activated protein kinase p38, both of which are capable of cleaving Bid, were detected in rd retinas at the peak time of photoreceptor death. In addition, the activated form of the cell death effector caspase-3 was detectable particularly at the photoreceptors in parallel with this peak degenerative phase. These data suggest that activation of both major apoptotic pathways occurs during photoreceptor degeneration in the rd mouse model of inherited blindness.
AB - Apoptosis is considered to be the final common pathway of photoreceptor cell death in different inherited retinal diseases. However, apoptosis encompasses diverse pathways of molecular interactions culminating in cellular demise. To begin dissecting these interactions, we have investigated key participants in the rd (retinal degeneration) model of retinal neurodegeneration. By Western blot analysis and immunocytochemistry, we found that cytochrome c release occurs in rd retinas concurrently with the activation of the proapoptotic protein Bid. Active forms of caspase-8 and the mitogen-activated protein kinase p38, both of which are capable of cleaving Bid, were detected in rd retinas at the peak time of photoreceptor death. In addition, the activated form of the cell death effector caspase-3 was detectable particularly at the photoreceptors in parallel with this peak degenerative phase. These data suggest that activation of both major apoptotic pathways occurs during photoreceptor degeneration in the rd mouse model of inherited blindness.
UR - http://www.scopus.com/inward/record.url?scp=0035159897&partnerID=8YFLogxK
U2 - 10.1006/mcne.2001.1036
DO - 10.1006/mcne.2001.1036
M3 - Article
VL - 18
SP - 335
EP - 346
JO - Molecular and Cellular Neurosciences
JF - Molecular and Cellular Neurosciences
IS - 4
ER -