computational insights on the competing effects of nitric oxide in regulating apoptosis计算的见解在竞争一氧化氮在调节细胞凋亡的影响.pdf

Computational Insights on the Competing Effects of Nitric Oxide in Regulating Apoptosis 1,2 3,4 3 5 1 Elife Z. Bagci , Yoram Vodovotz , Timothy R. Billiar , Bard Ermentrout *, Ivet Bahar * 1 Department of Computational Biology, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America, 2 Department of Biochemistry and Molecular Genetics, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America, 3 Department of Surgery, School of Medicine, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America, 4 Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America, 5 Department of Mathematics, Arts Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America Abstract Despite the establishment of the important role of nitric oxide (NO) on apoptosis, a molecular- level understanding of the origin of its dichotomous pro- and anti-apoptotic effects has been elusive. We propose a new mathematical model for simulating the effects of nitric oxide (NO) on apoptosis. The new model integrates mitochondria-dependent apoptotic pathways with NO-related reactions, to gain insights into the regulatory effect of the reactive NO species N O , non-heme 2 3 iron nitrosyl species (FeLnNO), and peroxynitrite (ONOO2). The biochemical pathways of apoptosis coupled with NO-related