rhEPO affects apoptosis in hippocampus of aging rats by upregulating SIRT1.
The aim of this study was to elucidate the signaling pathway involved in the anti-aging effect of erythropoietin (EPO) and to clarify whether recombinant human EPO (rhEPO) affects apoptosis in the aging rat hippocampus by upregulating Sirtuin 1 (SIRT1). In this study, a rat model of aging was established using D-galactose. Behavioral changes were monitored by the Morris water maze test. Using immunohistochemistry, we studied the expression of SIRT1, B-cell lymphoma/leukemia-2 gene (Bcl-2), and Bcl-2 associated X protein (Bax) expression, and apoptotic cells in the hippocampus of a rat model of aging in which rhEPO was intraperitoneally injected. The escape latency in rats from the EPO group shortened significantly; however, the number of platform passes increased significantly from that in the D-gal group (P < 0.05). Compared to the D-gal group, in the EPO group, the number of SIRT1 and Bcl-2-positive cells increased (P < 0.05), but the number of Bax-positive cells and apoptotic cells decreased in the hippocampus of aging rats (P < 0.05). These results suggest that rhEPO regulates apoptosis-related genes and affects apoptosis in the hippocampus of aging rats by upregulating SIRT. This may be one of the important pathways underlying the anti-aging property of EPO.
Department of Neurology, Second Affiliated Hospital of Medical College, Xi'an Jiaotong University Xi'an 710004, China.
Haiqin
H
Wu
Department of Neurology, Second Affiliated Hospital of Medical College, Xi'an Jiaotong University Xi'an 710004, China.
Huqing
H
Wang
Department of Neurology, Second Affiliated Hospital of Medical College, Xi'an Jiaotong University Xi'an 710004, China.
Wenting
W
Zhang
Department of Neurology, Second Affiliated Hospital of Medical College, Xi'an Jiaotong University Xi'an 710004, China.
Xuanhui
X
Wei
Department of Neurology, Second Affiliated Hospital of Medical College, Xi'an Jiaotong University Xi'an 710004, China.
Jiaxin
J
Zhao
Department of Neurology, Second Affiliated Hospital of Medical College, Xi'an Jiaotong University Xi'an 710004, China.
Pu
P
Yan
Department of Neurology, Second Affiliated Hospital of Medical College, Xi'an Jiaotong University Xi'an 710004, China.
Chao
C
Liu
D000367:Age Factors; D000375:Aging / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology*; D005690:Galactose / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494828:Bax protein, rat; C554270:EPO protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D051028:bcl-2-Associated X Protein; D004921:Erythropoietin; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D005690:Galactose
B-cell lymphoma/leukemia-2 gene; Bcl-2 association X protein; Erythropoietin; Sirtuin 1; aging