Elevation of cytoskeletal protein breakdown in aged Wistar rat brain.
Previous studies indicated there is an overall increase of proteolysis in aging rat brains. We monitored the potential degradation of cytoskeletal proteins in neuronal tissue taken from cerebral cortex and cerebellum of young (3 month) and aging (17, 21 and 23.5 month) Wistar rats. We found significant age-dependent proteolysis of cytoskeletal proteins (alphaII-spectrin and microtubule-associated protein MAP-2A/B) in the cerebral cortex and the cerebellum. The pattern of alphaII-spectrin breakdown shows a marked increase in 150- and 145-kDa fragments (SBDP150 and SBDP145, respectively), but we did not detect the caspase-3-mediated 120-kDa fragment (SBDP120) in aged rat brains, suggesting the involvement of the calpain proteases. The pattern of MAP-2A/B breakdown in aged rat brains mirrors that produced by in vitro calpain digestion of 3-month control rat brain MAP-2A/B. In aged rat brains, there is no significant increase in pro-caspase-3 processing; rather, there is a moderate reduction in pro-caspase-3 protein and caspase-3 hydrolytic activity in the cortex. These results point to selective susceptibility of cytoskeletal proteins to calpain-mediated degradation, but not caspase-3 in aging rat brains.
Bernath
Eric
E
Department of Neuroscience, McKnight Brian Institute, L4-100, P.O. Box 100256, University of Florida, Gainesville, FL 32610, USA.
Kupina
Nancy
N
Liu
Ming Cheng
MC
Hayes
Ronald L
RL
Meegan
Colleen
C
Wang
Kevin K W
KK
D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001923:Brain Chemistry / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000145:classification / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D003598:Cytoskeletal Proteins; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases