Mahendra Prasad Bhatt (강원대학교 의과대학) | 한빛사논문 > 한빛사

구.추천논문

조회3,994

강원대학교 의과대학

CV File 89 kb

Diabetes, January 2013 vol. 62 no. 1 243-253, doi: 10.2337/db12-0293 C-Peptide Prevents Hyperglycemia-Induced Endothelial Apoptosis Through Inhibition of Reactive Oxygen Species–Mediated Transglutaminase 2 Activation

Abstract

Mahendra Prasad Bhatt^1,2, Young-Cheol Lim¹, JongYun Hwang³, SungHun Na³, Young-Myeong Kim¹ and Kwon-Soo Ha¹

¹Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea
²Department of Laboratory Medicine, Gandaki Medical College Charak Hospital, Pokhara, Nepal
³Department of Obstetrics and Gynecology, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea

Corresponding author: Kwon-Soo Ha

Abstract
C-peptide is a bioactive peptide with a potentially protective role in diabetes complications; however, its molecular mechanism of protection against cardiovascular damage caused by hyperglycemia-induced apoptosis remains unclear. We investigated the protective mechanism of C-peptide against hyperglycemia-induced apoptosis using human umbilical vein endothelial cells and streptozotocin diabetic mice. High glucose (33 mmol/L) induced apoptotic cell death in endothelial cells via sequential elevation of intracellular Ca²⁺ and reactive oxygen species (ROS) as well as subsequent activation of transglutaminase 2 (TG2). C-peptide (1 nmol/L) prevented endothelial cell death by inhibiting protein kinase C- and NADPH oxidase-dependent intracellular ROS generation and by abolishing high glucose-induced TG2 activation, without affecting intracellular Ca²⁺ levels. Consistently, in the aorta of streptozotocin diabetic mice, hyperglycemia stimulated transamidating activity and endothelial cell apoptosis that was inhibited by C-peptide replacement therapy (35 pmol/min/kg) using osmotic pumps (control and diabetes, n = 8; diabetes + C-peptide, n = 7). In addition, C-peptide prevented hyperglycemia-induced activation of transamidation activity and apoptosis in the heart and renal cortex of streptozotocin diabetic mice. Thus, C-peptide protects endothelial cells from hyperglycemia-induced apoptotic cell death by inhibiting intracellular ROS-mediated activation of TG2. Furthermore, TG2 may be a promising avenue of therapeutic investigation to treat diabetic vasculopathies.

논문정보

형식Research article
게재일2013년 01월 (BRIC 등록일 2013-01-28)
연구진국내(교신)+국외 연구진
분야
구분구・추천논문

댓글 작성 로그인

CV 열람하기

연락처 보기