Alterations in calcium signaling and a decrease in Bcl-2 expression: possible correlation with apoptosis in aged striatum.
Aging is a multifaceted process associated with various functional and structural deficits that might be evolved in degenerative diseases. It has been shown that neurodegenerative disorders are associated with alterations in Ca(2+) homeostasis. Thus, in the present work, we have investigated Ca(2+) signaling and apoptosis in aged striatum. Our results show that glutamate and NMDA evoke a greater Ca(2+) rise in striatum slices from aged animals. However, this difference is not present when glutamate is tested in the absence of external Ca(2+). Immunostaining of glutamate receptors shows that only NMDA receptors (NR1) are increased in the striatum of aged rats. Increases in mitochondrial Ca(2+) content and in the reactive oxygen species levels were also observed in aged animals, which could be associated with tissue vulnerability. In addition, a decrease in the Bcl-2 protein expression and an enhancement in apoptosis were also present in aged striatum. Together the results indicate that, in aged animals, alterations in Ca(2+) handling coupled to an increase in ROS accumulation and a decrease in the prosurvival protein Bcl-2 may contribute to apoptosis induction and cell death in rat striatum.
Ureshino
R P
RP
Department of Pharmacology, Federal University of São Paulo, São Paulo, Brazil.
Bertoncini
C R
CR
Fernandes
M J S
MJ
Abdalla
F M F
FM
Porto
C S
CS
Hsu
Y-T
YT
Lopes
G S
GS
Smaili
S S
SS
D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D003342:Corpus Striatum / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D018698:Glutamic Acid / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D008928:Mitochondria / Q000502:physiology; D016202:N-Methylaspartate / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494828:Bax protein, rat; C409466:NR1 NMDA receptor; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D051028:bcl-2-Associated X Protein; D018698:Glutamic Acid; D016202:N-Methylaspartate; D002118:Calcium