Submitted on January 12, 2006
Accepted on July 30, 2006
Differential regulation of B/K protein expression in proximal and distal tubules of rat kidneys with ischemia-reperfusion injury
Ki-Hwan Han1, U-Young Lee2, Yoon-Seong Jang3, Yoon Mi Cho3, Young Min Jang3, In-A Hwang1, Jung Yeon Ghee4, Sun-Woo Lim4, Wan-Young Kim2, Chul-Woo Yang4, Jin Kim2*, and Oh-Joo Kwon3
1 Anatomy, College of Medicine, Ewha Womans University, Seoul, Korea, Republic of
2 Anatomy, College of Medicine, The Catholic University of Korea, Seoul, Korea, Republic of; MRC for Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea, Republic of
3 Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, Korea, Republic of; MRC for Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea, Republic of
4 Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea, Republic of; MRC for Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea, Republic of
* To whom correspondence should be addressed. E-mail: jinkim{at}catholic.ac.kr.
Brain/kidney (B/K) protein is a novel double C2-like-domain protein that is highly expressed in rat brain and kidney, but its cellular localization and functional role in the kidney are still undetermined. We examined the cellular localization of B/K protein in the rat kidney under normal and ischemic conditions. Ischemia-reperfusion (IR) injury was induced by clamping both renal arteries for 45 minutes, and animals were sacrificed at 1 and 6 hours and 1, 2, 3, 5, 7, 14, and 28 days after the reperfusion. Kidney tissues were processed for immunohistochemistry and immunoblot analyses using rabbit anti-B/K polyclonal antibodies. In control kidneys, B/K protein was expressed primarily in the distal tubules including the thick ascending limb, distal convoluted and connecting tubules, and collecting duct. Notably, B/K protein was also expressed in the straight portion (S3 segment), but not in the S1 or S2, of the proximal tubules, and podocytes of the glomerulus. In rat kidneys with IR injury, expression of B/K protein was differentially regulated according to anatomical location. In the distal tubules, overall expression of B/K protein was markedly decreased. On the other hand, IR injury significantly increased B/K protein expression in the S3 segment of the outer medulla as well as in rat proximal tubular epithelial cell line NRK-52E in vitro. Furthermore, B/K protein was strongly expressed in many exfoliated cells in the lumen and urine. These findings suggest that B/K protein is closely associated with cell death of the proximal tubules which are vulnerable to IR injury in kidney.
