The Protective Role of Heme Oxygenase-1 in Cerebral Ischemia

Abstract

Cerebral ischemia is one of the leading causes of death and disability in industrialized countries, with no curative treatments to date. Identification of potential targets and elucidation of their physiological role under stress conditions may give support to the development of drugs and strategies to contend with this pathology. In the last years, Heme oxygenase-1 (HO-1) has been considered by many groups as a potential target in ischemic damage. HO-1 is the enzyme responsible for the conversion of the heme group to billiverdin, carbon monoxide and iron; a highly regulated cytoprotective enzyme able to respond to numerous chemical or physical stressors, many of which decrease oxygen availability and generate oxidative stress. The disruption of HO-1 activity has been widely associated with a bad outcome in many disorders, and a protective role through its heme catabolism products has been observed in transplantation, cardiac ischemia, limb ischemia/reperfusion and different alterations that involve ischemia and reperfusion events. Here, we review recent reports supporting the protective role of HO-1 in cerebral ischemia. Results on the endogenous HO-1 response, overexpression of HO-1 and compounds that reduce ischemic damage through the induction of HO-1 in cerebral ischemia in in vivo and in vitro models are analyzed.

Global Transcriptomic Profiling of Cortex and Striatum: Cerebral Injury after Ischemia/Reperfusion in a Mouse Model

“…Reportedly, Hmox1 plays a protective role via its heme catabolism products in cerebral ischemia, cardiac ischemia, limb I/R, hepatic I/R, as well as transplantation that involves I/R events. 21 We found that Hmox1 was significantly upregulated in both cortex and striatum of I/R mice at 2, 8, and 24 hours post I/R. Although this result was inconsistent with previous studies, 21,22 Hmox1 might take part in the development of cortex and striatum injury after cerebral I/R.…”

Exercise preconditioning improves traumatic brain injury outcomes

“…HO-1 is a neuroprotective enzyme that exhibits anti-oxidative and anti-inflammatory effects (Aztatzi-Santillan et al, 2010; Bae et al, 2010). HO-1 mRNA and protein expression increase in the brain of mice after TBI (Anderson et al, 2009).…”

“…HO-1 plays a neuroprotective role in other pathophysiological conditions including; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridinium (MPP+) neurotoxicity (Bae et al, 2010), and stroke (Shah et al, 2010). Disrupting endogenous HO-1 responses has been associated with poor outcomes in many central nervous system disorders (Aztatzi-Santillan et al, 2010). …”

Protection against Heme Toxicity: Hemopexin Rules, OK?

“…185 There is no doubt that there is an important protective role for HOs in ICH, but mice studies have proven less than definitive as to the relative roles of the constitutively expressed heme oxygenase-2 (HO2) and the readily induced HO1. For example, HO2 ko mice appear to be more susceptible to damage after ICH than HO1 ko mice, 186,187 whereas HO1 deficiency leads to more damage in an ischemic stroke mouse model than does HO2 deficiency.…”