The role of globins in cardiovascular physiology

2021 ◽  
Author(s):  
T.C. Steven Keller ◽  
Christophe Lechauve ◽  
Alexander S Keller ◽  
Steven Brooks ◽  
Mitchell J Weiss ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Central Nervous System ◽  
Nervous System ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cell Types ◽  
Specific Cell ◽  
In Cells

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.

scholarly journals Spatially selective myosin regulatory light chain regulation is absent in dedifferentiated vascular smooth muscle cells but is partially induced by fibronectin and Klf4

2019 ◽  
Vol 316 (4) ◽  
pp. C509-C521 ◽  
Author(s):  
Tsubasa S. Matsui ◽  
Shinji Deguchi
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Light Chain ◽  
Muscle Cells ◽  
Cell Types ◽  
Myosin Regulatory Light Chain ◽  
Phosphorylation State ◽  
Spatial Regulation

The phosphorylation state of myosin regulatory light chain (MRLC) is central to the regulation of contractility that impacts cellular homeostasis and fate decisions. Rho-kinase (ROCK) and myosin light chain kinase (MLCK) are major kinases for MRLC documented to selectively regulate MRLC in a subcellular position-specific manner; specifically, MLCK in some nonmuscle cell types works in the cell periphery to promote migration, while ROCK does so at the central region to sustain contractility. However, it remains unclear whether or not the spatially selective regulation of the MRLC kinases is universally present in other cell types, including dedifferentiated vascular smooth muscle cells (SMCs). Here, we demonstrate the absence of the spatial regulation in dedifferentiated SMCs using both cell lines and primary cells. Thus, our work is distinct from previous reports on cells with migratory potential. We also observed that the spatial regulation is partly induced upon fibronectin stimulation and Krüppel-like factor 4 overexpression. To find clues to the mechanism, we reveal how the phosphorylation state of MRLC is determined within dedifferentiated A7r5 SMCs under the enzymatic competition among three major regulators ROCK, MLCK, and MRLC phosphatase (MLCP). We show that ROCK, but not MLCK, predominantly regulates the MRLC phosphorylation in a manner distinct from previous in vitro-based and in silico-based reports. In this ROCK-dominating cellular system, the contractility at physiological conditions was regulated at the level of MRLC diphosphorylation, because its monophosphorylation is already saturated. Thus, the present study provides insights into the molecular basis underlying the absence of spatial MRLC regulation in dedifferentiated SMCs.

scholarly journals Glucocorticoids stimulate collagen and noncollagen protein synthesis in cultured vascular smooth muscle cells.

1984 ◽  
Vol 98 (2) ◽  
pp. 541-549 ◽  
Author(s):  
D C Leitman ◽  
S C Benson ◽  
L K Johnson
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Specific Activity ◽  
Fold Increase ◽  
Muscle Cells ◽  
Type I ◽  
Twofold Increase ◽  
In Cells

The effect of glucocorticoids on collagen synthesis was examined in cultured bovine aortic smooth muscle (BASM) cells. BASM cells treated with 0.1 microM dexamethasone during their proliferative phase (11 d) were labeled with [3H]proline for 24 h, and the acid-precipitable material was incubated with bacterial collagenase. Dexamethasone produced an approximate twofold increase in the incorporation of proline into collagenase-digestible protein (CDP) and noncollagen protein (NCP) in the cell layer and medium. The stimulation was present in both primary mass cultures and cloned BASM. An increase in CDP and NCP was detected at 0.1 nM, while maximal stimulation occurred at 0.1 microM. Only cells exposed to dexamethasone during their log phase of growth (1-6 d after plating) showed the increase in CDP and NCP when labeled 11 d after plating. The stimulatory effect was observed in BASM cells treated with the natural bovine glucocorticoid, cortisol, dexamethasone, and testosterone, but was absent in cells treated with aldosterone, corticosterone, cholesterol, 17 beta-estradiol, and progesterone. The increase in CDP and NCP was absent in cells treated with the inactive glucocorticoid, epicortisol, and totally abolished by the antagonist, 17 alpha-hydroxyprogesterone, suggesting that the response was mediated by specific cytoplasmic glucocorticoid receptors. Dexamethasone-treated BASM cells showed a 4.5-fold increase in the specific activity of intracellular proline, which was the result of a twofold increase in the uptake of proline and depletion of the total proline pool. After normalizing for specific activity, dexamethasone produced a 2.4- and 2.8-fold increase in the rate of collagen and NCP synthesis, respectively. Cells treated with dexamethasone secreted 1.7-fold more collagen protein in 24 h compared to control cultures. The BASM cells secreted 70% Type I and 30% Type III collagen into the media as assessed by two-dimensional gel electrophoresis. The ratio of these two types was not altered by dexamethasone. The results of the present study demonstrate that glucocorticoids can act directly on vascular smooth muscle cells to increase the synthesis and secretion of collagen and NCP.

Regulation of calcium-activated chloride channels in smooth muscle cells: a complex picture is emerging

2005 ◽  
Vol 83 (7) ◽  
pp. 541-556 ◽  
Author(s):  
Normand Leblanc ◽  
Jonathan Ledoux ◽  
Sohag Saleh ◽  
Amy Sanguinetti ◽  
Jeff Angermann ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Chloride Channels ◽  
Muscle Cells ◽  
Cell Types ◽  
Dependent Protein Kinase ◽  
Intracellular Ca ◽  
Dependent Protein

Calcium-activated chloride channels (ClCa) are ligand-gated anion channels as they have been shown to be activated by a rise in intracellular Ca2+ concentration in various cell types including cardiac, skeletal and vascular smooth muscle cells, endothelial and epithelial cells, as well as neurons. Because ClCa channels are normally closed at resting, free intracellular Ca2+ concentration (~100 nmol/L) in most cell types, they have generally been considered excitatory in nature, providing a triggering mechanism during signal transduction for membrane excitability, osmotic balance, transepithelial chloride movements, or fluid secretion. Unfortunately, the genes responsible for encoding this class of ion channels is still unknown. This review centers primarily on recent findings on the properties of these channels in smooth muscle cells. The first section discusses the functional significance and biophysical and pharmacological properties of ClCa channels in smooth muscle cells, and ends with a description of 2 candidate gene families (i.e., CLCA and Bestrophin) that are postulated to encode for these channels in various cell types. The second section provides a summary of recent findings demonstrating the regulation of native ClCa channels in vascular smooth muscle cells by calmodulin-dependent protein kinase II and calcineurin and how their fine tuning by these enzymes may influence vascular tone. Key words: calcium-activated chloride channels, vascular smooth muscle cells, ion channels, calmodulin-dependent protein kinase II, calcineurin

Neuropeptide Y (NPY) and NPY receptors in the cardiovascular system: implication in the regulation of intracellular calciumThis paper is one of a selection of papers published in this Special Issue, entitled Young Investigators' Forum.

2007 ◽  
Vol 85 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Danielle Jacques ◽  
Dima Abdel-Samad
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Neuropeptide Y ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cell Types ◽  
Heart Cells ◽  
Microscopy Technique ◽  
Intracellular Ca

The 3-dimensional confocal microscopy technique has allowed us to identify the presence of yet another cardioactive factor and its receptor, namely neuropeptide Y (NPY) and its Y1 receptor, at the level of vascular smooth muscle cells and heart cells including endocardial endothelial cells (EECs). Using this technique, we also demonstrated that NPY is able to induce an increase in both cytosolic and nuclear calcium in all these cell types. Furthermore, besides being expressed at the level of EECs, NPY is also released from these cells following a sustained increase of intracellular Ca2+. This suggests the ability of NPY to contribute to the regulation of the excitation–secretion coupling of EECs and the excitation–contraction coupling of cardiomyocytes and vascular smooth muscle cells.

Mechanisms regulating the vascular smooth muscle Na/H exchanger (NHE-1) in diabetes

1998 ◽  
Vol 76 (5) ◽  
pp. 751-759 ◽  
Author(s):  
Katherine M Hannan ◽  
Peter J Little
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Hydrogen Exchange ◽  
Muscle Cells ◽  
Cell Types ◽  
Sodium Hydrogen ◽  
Sodium Hydrogen Exchanger ◽  
Multiple Cell

Vascular disease is a major component of the complications associated with diabetes. The pathology involves hypertrophy and proliferation of vascular smooth muscle cells and the production and modification of extracellular matrix. The sodium/hydrogen exchanger has been widely implicated in the growth of multiple cell types, including vascular smooth muscle. Increases in sodium/hydrogen exchange activity serve as an effector or at least as an indicator of vascular activation. This article is concerned with the role of the biochemical abnormalities of diabetes exerting their pathological effects on vascular smooth muscle cells via altering sodium/hydrogen exchange activity.Key words: diabetes, sodium/hydrogen exchanger, vascular smooth muscle, complications.

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