Does myoglobin protect Trypanosoma cruzi from the antiparasitic effects of nitric oxide?¹

Abstract

The hemoflagellate protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease, a progressive fatal cardiomyopathy widespread in South and Central America. Here, we postulate that the preferential colonization of cardiomyocytes by T. cruzi may reflect the role of myoglobin (Mb) as a nitric oxide (NO) scavenger, protecting the parasite from the trypanocidal effects of NO. The proposal of this novel function of Mb is based on knowledge that ferrous oxygenated Mb reacts rapidly and irreversibly with NO yielding nitrate and ferric oxidized Mb, which is reduced back to the physiologically active form by an intracellular reductase. The postulated protective role of Mb on the viability of T. cruzi is reminiscent of that postulated for hemoglobin in protecting intraerythrocytic Plasmodia from the parasiticidal effect of NO. ß

Unmasking the Janus face of myoglobin in health and disease

“…• (Ascenzi et al, 2001). In analogy, this phenomenon could also provide the base for the colonization of heart and skeletal muscles by T. gondii, an intracellular parasite, which is found worldwide (Ascenzi et al, 2005).…”

Nitric oxide dioxygenase function and mechanism of flavohemoglobin, hemoglobin, myoglobin and their associated reductases

“…Remarkably, Riggs [6] had anticipated a detoxification function analogous to the cytochrome P450s, superoxide dismutases, catalases and peroxidases in 1991, but the significance of Å NO as a substrate required time to be realized [61]. The NOD function of flavoHb and Hb has subsequently been confirmed, elaborated, expounded for Mb [38,[62][63][64], considered a ÔdeoxygenaseÕ [65] or possible dual function Å NO reductase-dioxygenase [66][67][68], and has been notably challenged [69] as broadly discussed in several recent reviews by others [7,8,30,67,68,70]. Arguments for an ancillary NAD(P)H-alkylhydroperoxide oxidoreductase or peroxidase function for flavoHbs have more recently surfaced [71,72], and other functions have been suggested.…”

Interaction and cystogenesis of Toxoplasma gondii within skeletal muscle cells in vitro

“…This is determined by the host immunosuppression, which leads to disruption of tissue cysts and subsequent bradyzoitetachyzoite conversion (Lyons et al 2002). A hypothesis was postulated linking the protective role of neuroglobin and myoglobin to the cytotoxic effect of nitric oxide, which is also observed during infection with Plasmodium and Trypanosoma cruzi in red blood cells and cardiomyocytes, respectively (Taylor-Robinson, 1998, Ascenzi et al 2001. In this context, these results could justify the persistence of T. gondii cysts in retina, in the nervous system and heart and skeletal muscles for a long time.…”