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1 College of Pharmacy, 2 School of Medicine, Pusan National University, Busan, Korea.
3 Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu, Korea.
4 Department of Cosmetology, Pusan Women's College, Busan, Korea.
5 Longevity Life Science & Technology Institute, Pusan National University, Busan, Korea.
6 Department of Physiology, University of Texas Health Science Center, San Antonio.
Address correspondence to Hae Young Chung, PhD, Longevity Life Science & Technology Institute, College of Pharmacy, Pusan National University, 30 Jangjun-dong, Gumjung-gu, Busan 609-735, Korea. E-mail: hyjung{at}pusan.ac.kr
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-B was analyzed, and greater activation of nuclear factor-B-inducing kinase (NIK)/IB kinase (IKK)/Inhibitor of B (IB) 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/IB/nuclear factor-B pathway brought on by oxidative stress.
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