Upregulation of aortic adhesion molecules during aging.
To investigate effects of aging on adhesion molecules (AMs), the present study assessed the expressions of aortic P-selectin and vascular adhesion molecule-1 (VCAM-1) in young (6-month-old) and old (24-month-old) Fischer 344 rats fed ad libitum (AL) or calorie-restricted diets. Results showed increased levels of aortic P-selectin and VCAM-1 in the old AL rats, causing excessive leukocyte infiltration as indicated by enhanced myeloperoxidase level. These elevations were parallel to increased oxidative stress including lipid peroxides during aging. Then involvement of redox-sensitive transcription factor nuclear factor-kappaB was analyzed, and greater activation of nuclear factor-kappaB-inducing kinase (NIK)/IkappaB kinase (IKK)/Inhibitor of kappaB (IkappaB) pathway in aorta from old AL rats was found. Further, in cultured endothelial cells challenged by various oxidative stimuli, the induced redox imbalance triggered overexpression and promoter activities of P-selectin and VCAM-1. Our study documented that aortic upregulated AMs with age are closely related to activation of NIK/IKK/IkappaB/nuclear factor-kappaB pathway brought on by oxidative stress.
College of Pharmacy, Pusan National University, Gumjung-gu, Busan 609-735, Korea.
Yani
Y
Zou
Sik
S
Yoon
Kyung Jin
KJ
Jung
Chul Hong
CH
Kim
Tae Gen
TG
Son
Min-Sun
MS
Kim
You Jung
YJ
Kim
Jaewon
J
Lee
Byung Pal
BP
Yu
Hae Young
HY
Chung
D000375:Aging / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism*; D015153:Blotting, Western; D031204:Caloric Restriction; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D051550:I-kappa B Kinase / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D019007:P-Selectin / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D015854:Up-Regulation / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; D009195:Peroxidase; D051550:I-kappa B Kinase