Detection of apoptosis in a rat model of focal cerebral ischemia using a homing peptide selected from in vivo phage display.
Focal cerebral ischemia, known as stroke, is caused by a sudden interruption in the blood supply to the brain. We attempted to identify peptides that can home to ischemic stroke tissue and detect the apoptosis of cells. A phage library displaying random peptides was screened for homing peptides to ischemic stroke tissue in a rat transient middle cerebral artery (MCA) occlusion model. After three rounds of in vivo screening, a phage clone displaying the most frequently occurring CLEVSRKNC sequence was selected. The CLEVSRKNC-phage preferentially homed to ischemic stroke tissue after intravenous administration into the MCA occlusion rats. The fluorescein-labeled synthetic CLEVSRKNC peptide, but not a scrambled control peptide, homed to ischemic stroke tissue with a lack of homing to non-ischemic brain tissue. The CLEVSRKNC peptide co-localized with a portion of neuronal cells, rather than with astrocytes, undergoing apoptosis at the penumbra region of stroke lesions. In autoradiographic studies, the uptake of the (131)I-labeled CLEVSRKNC peptide into an ischemic lesion increased at the first day and peaked at the third day after the injury. These results demonstrate that the CLEVSRKNC peptide can home to ischemic stroke tissue, while detecting apoptotic neuronal cells, and suggest it has applications as a targeting moiety for molecular imaging and selective drug delivery to stroke tissue.
Hong
Hai-Yan
HY
Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu 700-421, Republic of Korea.
Choi
Jung Sook
JS
Kim
Yoon Jung
YJ
Lee
Hwa Young
HY
Kwak
Wonjung
W
Yoo
Jeongsoo
J
Lee
Jae-Tae
JT
Kwon
Tae-Hwan
TH
Kim
In-San
IS
Han
Hyung-Soo
HS
Lee
Byung-Heon
BH
D000818:Animals; D017209:Apoptosis; D001345:Autoradiography; D017123:Bacteriophage T7 / Q000235:genetics; D002545:Brain Ischemia / Q000209:etiology* / Q000503:physiopathology*; D005822:Genetic Vectors; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage* / Q000378:metabolism; D019151:Peptide Library; D011868:Radioisotopes / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D009842:Oligopeptides; D019151:Peptide Library; D011868:Radioisotopes