Heme oxygenase activity in placenta: direct dependence on oxygen availability

Area of Science:

• Biochemistry
• Physiology
• Vascular Biology

Background:

• Carbon monoxide (CO), produced by heme oxygenase (HO), is implicated in vascular control.
• Hypoxia typically increases the expression of the inducible HO isoform (HO-1) at the mRNA and protein levels.
• It is commonly assumed that increased HO-1 expression leads to higher HO activity, but this requires verification due to oxygen's role in the catalytic process.

Purpose of the Study:

• To investigate whether low physiological oxygen concentrations limit heme oxygenase (HO) activity.
• To evaluate the relationship between oxygen availability and heme-derived carbon monoxide (CO) formation in human placental tissue.

Main Methods:

• Microsomal fractions from human placental chorionic villi were used.
• HO activity was measured by determining heme-derived CO formation.
• Samples were exposed to varying oxygen concentrations: 0%, 1%, 5%, and 21%.

Main Results:

• Heme oxygenase (HO) activity demonstrated a direct dependence on oxygen concentration.
• A progressive decrease in HO activity was observed as oxygen concentration decreased.
• This oxygen dependency of HO activity was consistent in placental villi from both preeclamptic and normotensive pregnancies.

Conclusions:

• Hypoxia's effect on HO activity is complex; while HO-1 expression may increase, the enzyme's catalytic function is constrained by oxygen availability.
• Oxygen concentration is a critical limiting factor for HO activity in human placental tissue.
• The findings challenge the assumption that increased HO-1 expression directly translates to increased HO activity under hypoxic conditions.