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Fig. 1. Oxygen signaling in neurons. Rapid responses to hypoxia are shown in red
and more slowly developing responses are shown in blue. (+) indicates a
potentiating effect on the target, (-) an inhibitory one. Oxygen interacts
with a variety of target molecules, both at the cell surface, e.g. ion
channels (see Table 1), NADPH
oxidase (Prabhakar and Overholt,
2000 ), cytosol, e.g. HIF and related proteins
(Semenza, 1999), and
organelles such as mitochondria. Decreases in oxygen tension have direct
effects on some ion channels (e.g. potassium channels, see references in
Table 1) and on molecules
associated with transcription factors such as HIF-1 . Hypoxia has
indirect effects mediated by changes in the bioenergetic state of mitochondria
via intermediate signaling modalities such as Ca2+
(Berridge et al., 2000;
Bickler et al., 2000) and
reactive oxygen species (ROS) (Haddad and
Land, 2000). Growth factors
(Nicole et al., 2001),
cytokines and inorganic ions (Millhorn et
al., 2000) may also modulate neuronal responses to hypoxia. Many
of these signals converge on MAP kinase cassettes including the ERK, JNK and
p38 pathways (Mattson, 1997;
Minet et al., 2000;
Semenza, 1999).
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