AJP-Lung Articles in PresS. Published on November 15, 2002 as DOI 10.1152/ajplung.00273.2002
1
BLEOMYCIN-INDUCED APOPTOSIS OF ALVEOLAR EPITHELIAL CELLS REQUIRES ANGIOTENSIN SYNTHESIS DE NOVO
Xiaopeng Li, Huiying Zhang, Valerie Soledad-Conrad, Jiaju Zhuang and Bruce D. Uhal
Department of Physiology, Michigan State University, East Lansing, Michigan, 48824
Running Head: ANGII Mediates Bleomycin-Induced Epithelial Apoptosis
Address all correspondence and reprint requests to: Bruce D. Uhal, Ph.D. Department of Physiology Michigan State University 3185 Biomedical and Physical Sciences Building East Lansing, MI 48824 Phone: (517)355-6475 x1144 Fax: (517)355-5125 Email:
[email protected]
Copyright 2002 by the American Physiological Society.
2 ABSTRACT Primary cultures of rat type II alveolar epithelial cells (AECs) or human AEC-derived A549 cells, when exposed to bleomycin (BLEO), exhibited concentration-dependent apoptosis detected by altered nuclear morphology, fragmentation of DNA, activation of Caspase 3 and net cell loss over time. In both cell culture models, exposure to BLEO caused time-dependent increases in angiotensinogen (ANGEN) mRNA. Antisense oligonucleotides against ANGEN mRNA inhibited BLEO-induced apoptosis of rat AEC or A549 cells by 83% and 84%, respectively (p
