Abstract
Outside their cellular environments, hemoglobin (Hb) and myoglobin (Mb) are known to wreak oxidative damage. Using haptoglobin (Hp) and hemopexin (Hx) the body defends itself against cell-free Hb, yet mechanisms of protection against oxidative harm from Mb are unclear. Mb may be implicated in oxidative damage both within the myocyte and in circulation following rhabdomyolysis. Data from the literature correlate rhabdomyolysis with the induction of Heme Oxygenase-1 (HO-1), suggesting that either the enzyme or its reaction products are involved in oxidative protection. We hypothesized that carbon monoxide (CO), a product, might attenuate Mb damage, especially since CO is a specific ligand for heme iron. Low density lipoprotein (LDL) was chosen as a substrate in circulation and myosin (My) as a myocyte component. Using oxidation targets, LDL and My, the study compared the antioxidant potential of CO in Mb-mediated oxidation with the antioxidant potential of Hp in Hb-mediated oxidation. The main cause of LDL oxidation by Hb was found to be hemin which readily transfers from Hb to LDL. Hp prevented heme transfer by sequestering hemin within the Hp-Hb complex. Hemin barely transferred from Mb to LDL, and oxidation appeared to stem from heme iron redox in the intact Mb. My underwent oxidative crosslinking by Mb both in air and under N2. These reactions were fully arrested by CO. The data are interpreted to suit several circumstances, some physiological, such as high muscle activity, and some pathological, such as rhabdomyolysis, ischemia/reperfusion and skeletal muscle disuse atrophy. It appear that CO from HO-1 attenuates damage by temporarily binding to deoxy-Mb, until free oxygen exchanges with CO to restore the equilibrium.
Highlights
Hemoglobin (Hb) and myoglobin (Mb) are the two major respiratory hemoproteins (RH) burdened with the task of maintaining aerobic life: Hb shuttles oxygen from the lungs to tissues, while Mb maintains a store of oxygen in muscles, ready for use
The current study further demonstrates that when a solution of cell-free Hb contains circulatory components of plasma, like hydrophobic Low density lipoprotein (LDL), hemin readily transfers from globin to these components
Hp acts by trapping the heme in the Hp-Hb complex, such that it can no longer oxidize LDL
Summary
Hemoglobin (Hb) and myoglobin (Mb) are the two major respiratory hemoproteins (RH) burdened with the task of maintaining aerobic life: Hb shuttles oxygen from the lungs to tissues, while Mb maintains a store of oxygen in muscles, ready for use Structural similarities in their globin (gl) backbones and a common ferrous heme iron at their active site indicate similar functionalities [1,2]. The auto-oxidation reaction generally yields a reactive oxygen species, like hydrogen peroxide, which goes on to wreak oxidative havoc in the cell: H2O+gl-FeII-O2Rgl-FeIII+ H2O2. This process is well documented in the literature [4]. Both RH possess redox activity based on FeIII to FeIV redox [2,3,4]
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