کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1958950 1057923 2006 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Bistability in Apoptosis: Roles of Bax, Bcl-2, and Mitochondrial Permeability Transition Pores
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Bistability in Apoptosis: Roles of Bax, Bcl-2, and Mitochondrial Permeability Transition Pores
چکیده انگلیسی

We propose a mathematical model for mitochondria-dependent apoptosis, in which kinetic cooperativity in formation of the apoptosome is a key element ensuring bistability. We examine the role of Bax and Bcl-2 synthesis and degradation rates, as well as the number of mitochondrial permeability transition pores (MPTPs), on the cell response to apoptotic stimuli. Our analysis suggests that cooperative apoptosome formation is a mechanism for inducing bistability, much more robust than that induced by other mechanisms, such as inhibition of caspase-3 by the inhibitor of apoptosis (IAP). Simulations predict a pathological state in which cells will exhibit a monostable cell survival if Bax degradation rate is above a threshold value, or if Bax expression rate is below a threshold value. Otherwise, cell death or survival occur depending on initial caspase-3 levels. We show that high expression rates of Bcl-2 can counteract the effects of Bax. Our simulations also demonstrate a monostable (pathological) apoptotic response if the number of MPTPs exceeds a threshold value. This study supports our contention, based on mathematical modeling, that cooperativity in apoptosome formation is critically important for determining the healthy responses to apoptotic stimuli, and helps define the roles of Bax, Bcl-2, and MPTP vis-à-vis apoptosome formation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 90, Issue 5, 1 March 2006, Pages 1546–1559
نویسندگان
, , , , ,