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New insights in prevention, diagnosis and treatment of stroke: its relation with atrial fibrillation
The role of hypoxia inducible factor 1 (HIF-1) in hypoxia induced apoptosis
Apoptosis can be induced in response to hypoxia. The
severity of hypoxia determines whether cells become
apoptotic or adapt to hypoxia and survive. A hypoxic
environment devoid of nutrients prevents the cell
undergoing energy dependent apoptosis and cells become
necrotic. Apoptosis regulatory proteins are delicately
balanced. In solid tumours, hypoxia is a common
phenomenon. Cells adapt to this environmental stress, so
that after repeated periods of hypoxia, selection for
resistance to hypoxia induced apoptosis occurs. These
resistant tumours probably have a more aggressive
phenotype and may have decreased responsiveness to
treatment. The key regulator of this process, hypoxia
inducible factor 1 (HIF-1), can initiate apoptosis by
inducing high concentrations of proapoptotic proteins,
such as BNIP3, and can cause stabilisation of p53.
However, during hypoxia, antiapoptotic proteins, such as
IAP-2, can be induced, whereas the proapoptotic protein
Bax can be downregulated. During hypoxia, an intricate
balance exists between factors that induce or counteract
apoptosis, or even stimulate proliferation. Understanding
the regulation of apoptosis during hypoxia and the
mechanisms of resistance to apoptosis might lead to more
specific treatments for solid tumours
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