Hypoxia: Exploring Early Manifestations and Therapeutic Possibilities

Tissue damage in many acute and chronic diseases is known to stem from hypoxia where oxygen deficiency and generation of excess reactive oxygen species (ROS) are two major sources of cell injury. Detecting and understanding the earliest manifestations of such injury is of prime interest from a therapeutic standpoint. Toward this direction, we have developed an in vitro model where hypoxic stress can be monitored at a high temporal resolution through real time observation of cellular morphodynamic properties. In this model, hypoxia is chemically induced in highly motile cervical cancer cells via exposure to sodium sulfite, which elicited a dose-dependent reduction of cell movement within minutes. This conspicuous change in cell motility is associated with a disruption of the actin cytoskeleton. Apart from investigating the molecular mechanism underlying such a change, we are using this model to evaluate novel approaches aimed to reduce hypoxia and oxidative stress-induced damage. We are currently exploring the possibility of microparticle-based cellular delivery of enzymes superoxide dismutase and catalase to reduce the ROS load in cells.