Oxyhemoglobin produces apoptosis and necrosis in cultured smooth muscle cells

Confluent rat aortic smooth muscle cells were treated with OxyHb in a conce ntration- and time-dependent manner. A high concentration of OxyHb (100 muM ) within 24 h decreased cell density. DNA analysis showed a smear pattern c haracteristics of cell necrosis. Transmission electron microscopy demonstra ted disintegration of the cell membrane and destruction of cell organelles. Western blotting using PARP antibody revealed that 116 kDa PARP was not cl eaved to 85 kDa, an apoptosis-related fragment. On the contrary, a low conc entration of OxyHb (10 muM) produced apoptotic cell death at 72 h that was supported by DNA analysis and TUNEL staining. These results demonstrated th at a high level of OxyHb induced necrosis within 24 h and a low concentrati on of OxyHb produced apoptosis after 72 h in cultured smooth muscle cells. Morphological alterations induced by OxyHb might contribute to the vascular wall changes in the cerebral arteries following subarachnoid hemorrhage (S AH). (C) 2001 Elsevier Science B.V. All rights reserved.