Adaptive responses to tissue injury: role of heme oxygenase-1

Abstract

Tissue injury may result as a consequence of a physical, chemical, or biological insult. Such injury recruits an adaptive response to restore homeostasis and protect against further injury. One of the most prompt protective and adaptive responses by all tissues is the robust activation of the highly inducible, anti-inflammatory, anti-oxidant, and anti-apoptotic protein, heme oxygenase-1 (HO-1). HO-1, a microsomal enzyme, catalyzes the breakdown of pro-oxidant heme, which is released from heme proteins to equimolar quantities of iron, carbon monoxide, and biliverdin. Biliverdin is converted to bilirubin by biliverdin reductase. The beneficial effects of HO-1 expression are not merely due to heme degradation but are also attributed to the cytoprotective properties of the byproducts of the reaction. Manipulation of this enzymatic system in a myriad of disease models has provided substantial evidence to support its role as a cytoprotective enzyme and is therefore an emerging therapeutic molecule.

Fig. 1.

Enzymatic reaction catalyzed by heme oxygenase-1.

Fig. 2.

Number of publications from PubMed using the search term “heme oxygenase.”

Fig. 3.

Conditioned media (CM) from HO-1^+/+ mesenchymal stem cells (MSC) protects against cisplatin nephrotoxicity. (A) The amount of body weight loss following cisplatin administration was calculated and expressed as a percentage of the original weight. (B) Serum creatinine levels were measured and expressed as mg/dl. (C) Western blot analysis of cleaved caspase 3 expression in kidneys. Densitometric analysis of the bands on the caspase-3 and actin blots is indicated. Data are expressed as means ± SE and *P < 0.05. Reproduced with permission from Zarjou et al. (26).