The role of globins in cardiovascular physiology

Abstract

Globin proteins exist in every cell type of the vasculature, from erythrocytes to endothelial cells, vascular smooth muscle cells, and peripheral nerve cells. Many globin subtypes are also expressed in muscle tissues (including cardiac and skeletal muscle), in other organ-specific cell types, and in cells of the central nervous system. The ability of each of these globins to interact with molecular oxygen (O2) and nitric oxide (NO) is preserved across these contexts. Endothelial α-globin is an example of extra-erythrocytic globin expression. Other globins, including myoglobin, cytoglobin, and neuroglobin are observed in other vascular tissues. Myoglobin is observed primarily in skeletal muscle and smooth muscle cells surrounding the aorta or other large arteries. Cytoglobin is found in vascular smooth muscle but can also be expressed in non-vascular cell types, especially in oxidative stress conditions after ischemic insult. Neuroglobin was first observed in neuronal cells, and its expression appears to be restricted mainly to the central and peripheral nervous systems. Brain and central nervous system neurons expressing neuroglobin are positioned close to many arteries within the brain parenchyma and can control smooth muscle contraction and, thus, tissue perfusion and vascular reactivity. Overall, reactions between NO and globin heme-iron contribute to vascular homeostasis by regulating vasodilatory NO signals and scaveging reactive species in cells of the mammalian vascular system. Here, we discuss how globin proteins affect vascular physiology with a focus on NO biology, and offer perspectives for future study of these functions.

Biochemical and Genetic Markers in Neurological Trauma and Tumors: Review Article

“…Following ischemiarelated strain, every molecule which possess the ability to increase oxygen delivery or reduce reactive oxygen species -induced damage is supposed to improve cell survival. In agreement with this, many studies have shown that lowered Ngb amounts in experimental models hindered viability of cultured neuronal cells, whilst amplification of Ngb increased vitality [51,52].…”

Redox-Regulation of α-Globin in Vascular Physiology

“…Globin proteins in the cells of the vascular wall can regulate vasodilatory NO signaling between endothelium and smooth muscle [ 10 , 11 , 12 , 13 , 14 , 41 , 42 ]. Each globin has unique properties with respect to regulating NO/nitrite/nitrate and O 2 affinity [ 9 ]; however, to provide a continuous reserve of NO scavenging (through dioxygenation, in normoxic conditions) or production (nitrite reductase, in hypoxic conditions), oxidized (Fe 3+ ) globin needs to be recycled to the (Fe 2+ ) globin reduced state. In the myoendothelial junctions (MEJs) of ECs, oxygenated (Fe 2+ ) α-globin bound to eNOS promotes vasoconstriction by degrading locally produced NO to generate NO 3 − and oxidized (Fe 3+ ) α-globin, which is unable to degrade NO further [ 11 , 28 ].…”

“…These globins, particularly cytoglobin, may serve as reversible ligand carriers and may also participate in redox reactions, but their biological functions are currently unclear [ 7 ]. Each member of the globin family of proteins has a distinct pattern of tissue expression, subcellular localization, and affinity for external ligands, including O 2 , carbon dioxide (CO 2 ), and NO [ 8 , 9 ]. Globin proteins in the cells of the vascular wall can regulate vasodilatory NO signaling between endothelium and smooth muscle, inactivating and detoxifying NO by transforming it to nitrate (NO 3 − ) or reducing nitrite (NO 2 − ) to active NO under hypoxic conditions to enable autoregulation of tissue perfusion by smooth muscle [ 9 ].…”

Designing Artificial Metalloenzymes by Tuning of the Environment beyond the Primary Coordination Sphere

“…While undeniably important, abundant evidence from the study of metalloenzymes has shown that the same PCS environment, such as heme b , can display a variety of different properties from electron transfer to reversible O 2 binding, dioxygen reduction, and small molecule functionalization . As a result, these heme proteins perform a wide range of biological processes, including O 2 transport (globins), − cell signaling, − electron transfer, − and enzymatic activities such as catalases, − oxidases, , oxygenases, − peroxidases, − nitric oxide reductases, − and sulfite reductases. − Therefore, features of the protein environment beyond the PCS are essential in not only fine-tuning the activities of metalloenzymes but also conferring new activities in otherwise similar systems.…”