The appearance of photosynthetic organisms about 3 billion years ago increased
the partial pressure of oxygen (PO2) in the atmosphere and enabled the evolution of
organisms that use glucose and oxygen to produce ATP by oxidative phosphorylation.
Hypoxia is commonly defined as the reduced availability of oxygen in the tissues
produced by different causes, which include reduction of atmospheric PO2 as in
high altitude, and secondary to pathological conditions such as sleep breathing and
pulmonary disorders, anemia, and cardiovascular alterations leading to inadequate
transport, delivery, and exchange of oxygen between capillaries and cells. Nowadays,
it has been shown that hypoxia plays an important role in the genesis of several
human pathologies including cardiovascular, renal, myocardial and cerebral diseases
in fetal, young and adult life.
Several mechanisms have evolved to maintain oxygen homeostasis. Certainly, all
cells respond and adapt to hypoxia, but only a few of them can detect hypoxia and
initiate a cascade of signals intended to produce a functional systemic response.
In mammals, oxygen detection mechanisms have been extensively studied in
erythropoietin-producing cells, chromaffin cells, bulbar and cortical neurons,
pulmonary neuroepithelial cells, smooth muscle cells of pulmonary arteries, and
chemoreceptor cells. While the precise mechanism underpinning oxygen, sensing
is not completely known several molecular entities have been proposed as possible
oxygen sensors (i.e. Hem proteins, ion channels, NADPH oxidase, mitochondrial
cytochrome oxidase). Remarkably, cellular adaptation to hypoxia is mediated by
the master oxygen-sensitive transcription factor, hypoxia-inducible factor-1, which
can induce up-regulation of different genes to cope the cellular effects related
to a decrease in oxygen levels. Short-term responses to hypoxia included mainly
chemoreceptor-mediated reflex ventilatory and hemodynamic adaptations to
manage the low oxygen concentration while more prolonged exposures to hypoxia
can elicit more sustained physiological responses including switch from aerobic
to anaerobic metabolism, vascularization, and enhancement of blood O2 carrying
capacity.
The focus of this research topic is to provide an up-to-date vision on the current
knowledge on oxygen sensing mechanism, physiological responses to acute or
chronic hypoxia and cellular/tissue/organ adaptations to hypoxic environment.