Biological signaling by carbon monoxide and carbon monoxide-releasing molecules

Abstract

Carbon monoxide (CO) is continuously produced in mammalian cells during the degradation of heme. It is a stable gaseous molecule that reacts selectively with transition metals in a specific redox state, and these characteristics restrict the interaction of CO with defined biological targets that transduce its signaling activity. Because of the high affinity of CO for ferrous heme, these targets can be grouped into heme-containing proteins, representing a large variety of sensors and enzymes with a series of diverse function in the cell and the organism. Despite this notion, progress in identifying which of these targets are selective for CO has been slow and even the significance of elevated carbonmonoxy hemoglobin, a classical marker used to diagnose CO poisoning, is not well understood. This is also due to the lack of technologies capable of assessing in a comprehensive fashion the distribution and local levels of CO between the blood circulation, the tissue, and the mitochondria, one of the cellular compartments where CO exerts its signaling or detrimental effects. Nevertheless, the use of CO gas and CO-releasing molecules as pharmacological approaches in models of disease has provided new important information about the signaling properties of CO. In this review we will analyze the most salient effects of CO in biology and discuss how the binding of CO with key ferrous hemoproteins serves as a posttranslational modification that regulates important processes as diverse as aerobic metabolism, oxidative stress, and mitochondrial bioenergetics.

Study of the cytotoxic and genotoxic potential of the carbonyl ruthenium(II) compound, ct‐[RuCl(CO)(dppb)(bipy)]PF6 [dppb = 1,4‐bis(diphenylphosphino)butane and bipy = 2,2′‐bipyridine], by in vitro and in vivo assays

“…Some studies have demonstrated the selective interaction of CO with structural and functional proteins, for example the interaction of CO with iron and heme‐dependent proteins (Wilkinson & Kemp, ). However, systems containing transition metals may preferentially potentiate the biological activity of the CO molecule (Motterlini & Foresti, ), as is the case of the ruthenium carbonyl compound studied. Our research group evaluated the release of the CO molecule from ct‐ [RuCl(CO)(dppb)(bipy)]PF 6 by 13 C{ 1 H} NMR (DMSO‐d 6 ) and cyclic voltammetry.…”

Anti-apoptotic properties of carbon monoxide in porcine oocyte duringin vitroaging

“…However, in the case of CORM-A1, we observed the effect of different concentrations. We attribute it to the different kinetics of CO release from CORM-A1 and CORM-2 (Motterline & Foresti, 2017). …”

Regulation of erythrocyte function: Multiple evolutionary solutions for respiratory gas transport and its regulation in fish

“…68 In view of these findings, Hb appears to play a part in NO-dependent signalling. 164 The overall picture that emerges is that gaseous signalling plays an important role in erythrocyte function and that Hb is important in its regulation. Another signalling molecule, hydrogen sulphide, has also been demonstrated to be especially important in regulating the vasculature in response to hypoxia.…”