Role of heme oxygenase-1 in transplantation

Abstract

Summary Heme oxygenase‐1 (HO‐1) is the rate‐limiting enzyme in heme catabolism that converts heme to Fe++, carbon monoxide and biliverdin. HO‐1 acts anti‐inflammatory and modulates apoptosis in many pathological conditions. In transplantation, HO‐1 is overexpressed in organs during brain death, when undergoing ischemic damage and rejection. However, intentionally induced, it ameliorates pathological processes like ischemia reperfusion injury, allograft, xenograft or islet rejection, facilitates donor specific tolerance and alleviates chronic allograft changes. We herein consistently summarize the huge amount of data on HO‐1 and transplantation that have been generated in multiple laboratories during the last 15 years and suggest possible clinical implications and applications for the near future.

ZnPP reduces autophagy and induces apoptosis, thus aggravating liver ischemia/reperfusion injury in vitro

“…It has been demonstrated that HO-1 induces autophagy in a mouse model of liver IR injury; however, the specific mechanisms involved require further investigation (35). It has also been previously demonstrated that HO-1 protein expression is induced in injured cells or cells under stess (26)(27)(28). In our study, this was achieved by treatment with mineral oil, which caused damage to the liver cells due to the lack of nutrients and oxygen.…”

“…Previous studies have shown that HO-1 plays a very important anti-inflammatory role in a number of inflammatory diseases, and it may act as an anti-apoptotic and anti-proliferative mediator for many damaged organs or cells under stress conditions (26)(27)(28). In liver cell injury, induced HO-1 preconditioning may lead to adaptive stress reaction, and may occur in response to organ ischemic insults, protecting the cells from injury (29,30).…”

The Introduction of Human Heme Oxygenase-1 and Soluble Tumor Necrosis Factor-α Receptor Type I With Human IgG1 Fc in Porcine Islets Prolongs Islet Xenograft Survival in Humanized Mice

“…HO-1 has antioxidant, antiapoptotic and anti-inflammatory effects (8) and improves outcomes for both islet allografts and xenografts (9,10). Tumor necrosis factor-a (TNF-a) is produced chiefly by activated macrophages, although it can be produced by other cell types such as CD4 þ T cells.…”

Mechanisms and Consequences of Injury and Repair in Older Organ Transplants

“…However, induction of HSPs during stress diminishes with aging (74) and is associated with increased injury (75). The protective capacity of HSP-32, or hemeoxygenase 1 (HO-1), has been comprehensively reviewed elsewhere (76). Briefly, while not having a chaperoning function, HO-1 exhibits anti-inflammatory, anti-oxidant, and anti-apoptotic properties (77).…”