Reactive oxygen species and possibly oxidized lipids, as described above, may have a central role in numerous mitochondria-related signaling pathways. Growth factors, inflammation-related factors, and reactive oxygen species can induce the production of ROS by mitochondria and the mechanisms described above, which in turn, induces subsequent steps in signaling pathways. These pathways induce responses which promote either cellular protection or cell death. Several cellular signaling pathways, which may be involved, include those activated by the vasoac-tive agents such as transforming growth factor (TGF)-[beta],90 epidermal growth factor (EGF),91 angiotensin II,92 and tumor necrosis factor (TNF)-[alpha].19,93,94 These pathways induce the production of ROS, which acts in the "transactivation" of growth factor receptors. The "transactivated" receptors induce protection against oxidative stress.95 The downstream ROS-activated pathways may involve the MAPK proteins, which includes several kinases such as p38 MAPK, c-jun N-terminal kinase, and extracellular signal-regulated kinases 1 and 2. Activation of these pathways by ROS can be cytoprotective, but the effect is dependent on cell type and conditions. Another cytoprotective pathway is a stimulation of ROS through angiotensin II activation of K channels in smooth muscle cells, which in turn activates MAPKs. Also, reactive oxygen species can react with RNS and form perox-ynitrite, which can induce AMPK, a central regulator of energy metabolism. Alternatively, mitochondrial ROS can promote cell proliferation and enhance DNA damage and angiogenesis, the later through decreased expression of MnSOD activity. ROS also can alter the regulation of MAPKs and matrix metalloproteinases and decrease cell survival. Thus, ROS can promote cellular damage and induce cellular apoptosis under certain circumstances. The mechanisms involved in the selection of the specific activity, cell death or protection, are unknown at this time.
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Metabolism. There isn’t perhaps a more frequently used word in the weight loss (and weight gain) vocabulary than this. Indeed, it’s not uncommon to overhear people talking about their struggles or triumphs over the holiday bulge or love handles in terms of whether their metabolism is working, or not.