Acute oxygen sensing in heme oxygenase-2 null mice

Area of Science:

• Physiology
• Biochemistry
• Molecular Biology

Background:

• Hemeoxygenase-2 (HO-2) is an antioxidant enzyme implicated in O(2) sensing.
• HO-2 has been proposed as the acute O(2) sensor in the carotid body (CB).
• Maxi-K(+) channels are involved in O(2) sensing.

Purpose of the Study:

• To investigate the physiological role of HO-2 in O(2) sensing using HO-2 null mice.
• To determine if HO-2 deficiency impacts the hypoxia sensitivity of the carotid body and adrenal medulla.

Main Methods:

• Utilized HO-2 null mice and their control littermates.
• Examined carotid body phenotype, including organ growth and gene expression.
• Assessed hypoxia responsiveness in carotid body and adrenal medulla cells.
• Investigated the effect of maxi-K(+) channel blockade with iberiotoxin.

Main Results:

• HO-2 deficiency resulted in carotid body growth and altered expression of stress-dependent genes, including the maxi-K(+) channel alpha-subunit.
• Hypoxia sensitivity of the carotid body was similar in HO-2 null mice and controls.
• Hypoxia response in carotid body and adrenal medulla cells was maintained despite HO-2 deficiency and maxi-K(+) channel blockade.
• Redox disregulation from HO-2 deficiency impacted maxi-K(+) channel gene expression but not intrinsic O(2) sensitivity.

Conclusions:

• HO-2 deficiency affects maxi-K(+) channel gene expression but does not alter the intrinsic O(2) sensitivity of carotid body or adrenal medulla cells.
• HO-2 is not a universally required acute O(2) sensor.
• The role of HO-2 in O(2) sensing requires further investigation, as other mechanisms likely contribute.