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Visualization of Vascular Ca2+ Signaling Triggered by Paracrine Derived ROS
Published on: December 21, 2011
Stochastic modelling suggests that an elevated superoxide anion - hydrogen peroxide ratio can drive extravascular
1Department of Biochemistry, Dr. Baba Saheb Ambedkar Medical College & Hospital, Government of NCT Delhi, Sector - 6, Rohini, Delhi 110085, India; Mathematical and Computational Biology, Information Technology Research Academy (ITRA), Media Lab Asia, 2nd Floor, Block 2, C-DOT Campus, Mehrauli, New Delhi 110030, India; School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Mehrauli Road, New Delhi 110067, India.
Abstract:
Chemotaxis, integrates diverse intra- and inter-cellular molecular processes into a purposeful patho-physiological response; the operatic rules of which, remain speculative. Here, I surmise, that superoxide anion induced directional motility, in a responding cell, results from a quasi pathway between the stimulus, surrounding interstitium, and its biochemical repertoire. The epochal event in the mounting of an inflammatory response, is the extravascular transmigration of a phagocyte competent cell towards the site of injury, secondary to the development of a lamellipodium. This stochastic-to-markovian process conversion, is initiated by the cytosolic-ROS of the damaged cell, but is maintained by the inverse association of a de novo generated pool of self-sustaining superoxide anions and sub-critical hydrogen peroxide levels. Whilst, the exponential rise of O2(.-) is secondary to the focal accumulation of higher order lipid raft-Rac1/2-actin oligomers; O2(.-) mediated inactivation and redistribution of ECSOD, accounts for the minimal concentration of H2O2 that the phagocyte experiences. The net result of this reciprocal association between ROS/ RNS members, is the prolonged perturbation and remodeling of the cytoskeleton and plasma membrane, a prelude to chemotactic migration. The manuscript also describes the significance of stochastic modeling, in the testing of plausible molecular hypotheses of observable phenomena in complex biological systems.

