Heme Oxygenase Biology: Part 2: Neonatal Disorders

Abstract

A number of neonatal disorders have etiologies originating from acute inflammation and the destructive action of reactive oxygen species. As previously described in Part 1, heme oxygenase (HO) and its byproducts provide a newborn with antioxidative, antiapoptotic, anti-inflammatory, and cytoprotective defenses during the perinatal period. A finely balanced expression of the inducible HO-1 isoform is critically important for normal development of a number of organs. For example, increases in bilirubin levels observed in newborn infants provide significant antioxidant protection at birth and during the first few weeks after birth. However, if not tightly controlled, harmful levels may be reached and cause irreversible bilirubin-induced neurotoxicity (kernicterus). In addition, HO-1 and the constitutive HO-2 isoform are important in pulmonary vascular development during the perinatal period. In the developing brain, the upregulation of HO-1 expression may be adaptive and beneficial or a part of a pathological inflammatory process. Furthermore, there is strong evidence that HO and its byproduct, carbon monoxide (CO), play a significant role in maintaining intestinal barrier function and regulating inflammatory and apoptotic pathways. Therefore, disruption of this balanced HO-1 expression may lead to a number of neonatal disorders.