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P13MITOCHONDRIAL-CYTONUCLEAR CROSSTALK AND OXIDO-REDUCTIVE STRESS IN HEART FAILURE

The eld of redo biology encompasses storied histories ranging from longstanding en-deavors on the o idative theory of aging to more recent fundamental advances of the dual speci city roles for R in disease pathogenesis and signaling pathways. otwithstand-ing, numerous clinical trials of therapeutic interventions for mitigating o idative stress have been uniformly disappointing and even deleterious. Both alterations of and, perhaps,

ADP homeostasis can tilt the redo status towards the reductive phase, which is critical-ly linked to survival and cell death pathways. ur recent studies have stimulated much in-terest to develop complementary model systems, mimicking e perimental reductive stress. This lecture will e plore the conceptual, biochemical and molecular conse uences - at the reductive ends of the redo spectrum- mediated by key effector pathways such as rf2.

ngoing and future studies are seeking to identify the genetic basis of clinical manifesta-tions linked to either increase susceptibility or resistance of o ido-reductive dysregulation. There is considerable e citement in the eld of redo biology that such advances could accelerate the pace for personalized medicine.

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P14ANTIOXIDANT TO PRO-OXIDANT THERAPY FOR CANCER

Cancer cells produce high levels of reactive o ygen species (R ), primarily supero ide and hydrogen pero ide. ncogene activation, coupled with the loss of tumor suppres-sors, promotes R production at mitochondria, endoplasmic reticulum and ADP o i-dases. The tumor microenvironment, characterized by low glucose, hypo ia and in am-matory in ltration, further increases R levels in cancer cells. Elevated R levels can hyper-activate multiple pathways (PI , MAP s, -ΚB, I s) that are known to be pro-tumorigenic. owever, uncontrolled o idant production is incompatible with cellular vi-ability. Thus, cancer cells have enhanced antio idant function which allows them to main-tain a balance between the growth-promoting and damage-inducing properties of R . I will discuss the current thinking regarding disabling cellular antio idants to increase R levels in cancer cells to levels that elicit damage and thus reduce tumor burden.

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doi: 10.1016/j.freeradbiomed.2013.10.408

doi: 10.1016/j.freeradbiomed.2013.10.407