Oxidative stress response and signaling in hematological malignancies and HIV infection.
Hematopoietic cells can be exposed to a wide spectrum of oxidative stresses. Excessive oxidative stress damages biomolecules such as DNA, proteins, and lipids, leading to cellular dysfunction and cell death. Accumulation of such damage provokes noxious effects on individuals, resulting in diseases such as hematopoietic malignancies. On the other hand, cells have multiple mechanisms to protect themselves from stress. These mechanisms include apoptosis, DNA repair, cell cycle regulation, and induction of antioxidant and detoxifying enzymes. Reactive oxygen species (ROS) may act as intracellular signaling mediators in physiological signal transduction. ROS activate cascades of events, such as activation of tyrosine kinases, small Ras proteins, and the mitogen-activated protein kinase system, followed by the activation of some subsets of transcription factors. Antioxidants are induced by oxidative stress to act not simply as scavengers of ROS but also as important regulators of oxidative stress response. Meanwhile, oxidative stress often causes apoptosis, in which mitochondrial control has been known to play an essential role. The dysregulation of antioxidants and apoptosis is deeply involved in the pathogenesis and pathophysiology of virus-associated hematopoietic disorders, including acquired immunodeficiency syndrome.