
Proceedings Paper
Hypothesis for thermal activation of the caspase cascade in apoptotic cell death at elevated temperaturesFormat | Member Price | Non-Member Price |
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Paper Abstract
Apoptosis is an especially important process affecting disease states from HIV-AIDS to auto-immune disease to
cancer. A cascade of initiator and executioner capsase functional proteins is the hallmark of apoptosis. When activated
the various caspases activate other caspases or cleave structural proteins of the cytoskeleton, resulting in "blebbing" of
the plasma membrane forming apoptotic bodies that completely enclose the disassembled cellular components.
Containment of the cytosolic components within the apoptotic bodies differentiates apoptosis from necroptosis and
necrosis, both of which release fragmented cytosol and other cellular constituents into the intracellular space.
Biochemical models of caspase activation reveal the extensive feedback loops characteristic of apoptosis. They
clearly explain the failure of Arrhenius models to give accurate predictions of cell survival curves in hyperthermic
heating protocols. Nevertheless, each of the individual reaction velocities can reasonably be assumed to follow
Arrhenius kinetics. If so, the thermal sensitivity of the reaction velocity to temperature elevation is: ∂k/∂T = Ea [k/RT2].
Particular reaction steps described by higher activation energies, Ea, are likely more thermally-sensitive than lower
energy reactions and may initiate apoptosis in the absence of other stress signals. Additionally, while the classical
irreversible Arrhenius formulation fails to accurately represent many cell survival and/or dye uptake curves - those that
display an early stage shoulder region - an expanded reversible model of the law of mass action equation seems to
prove effective and is directly based on a firm theoretical thermodynamic foundation.
Paper Details
Date Published: 26 February 2013
PDF: 9 pages
Proc. SPIE 8584, Energy-based Treatment of Tissue and Assessment VII, 85840K (26 February 2013); doi: 10.1117/12.2001663
Published in SPIE Proceedings Vol. 8584:
Energy-based Treatment of Tissue and Assessment VII
Thomas P. Ryan, Editor(s)
PDF: 9 pages
Proc. SPIE 8584, Energy-based Treatment of Tissue and Assessment VII, 85840K (26 February 2013); doi: 10.1117/12.2001663
Show Author Affiliations
John A. Pearce, The Univ. of Texas at Austin (United States)
Published in SPIE Proceedings Vol. 8584:
Energy-based Treatment of Tissue and Assessment VII
Thomas P. Ryan, Editor(s)
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