scholarly journals Vascular CaMKII: heart and brain in your arteries

2016 ◽  
Vol 311 (3) ◽  
pp. C462-C478 ◽  
Author(s):  
Fanny Toussaint ◽  
Chimène Charbel ◽  
Bruce G. Allen ◽  
Jonathan Ledoux
Keyword(s):  
Cellular Proliferation ◽  
Cell Function ◽  
Vascular System ◽  
Splice Variants ◽  
Cell Types ◽  
Cellular Functions ◽  
Vascular Cell ◽  
Calcium Calmodulin Dependent ◽  
Regulatory Processes ◽  
Neuronal Tissues

First characterized in neuronal tissues, the multifunctional calcium/calmodulin-dependent protein kinase II (CaMKII) is a key signaling component in several mammalian biological systems. Its unique capacity to integrate various Ca2+ signals into different specific outcomes is a precious asset to excitable and nonexcitable cells. Numerous studies have reported roles and mechanisms involving CaMKII in brain and heart tissues. However, corresponding functions in vascular cell types (endothelium and vascular smooth muscle cells) remained largely unexplored until recently. Investigation of the intracellular Ca2+ dynamics, their impact on vascular cell function, the regulatory processes involved and more recently the spatially restricted oscillatory Ca2+ signals and microdomains triggered significant interest towards proteins like CaMKII. Heteromultimerization of CaMKII isoforms (four isoforms and several splice variants) expands this kinase's peculiar capacity to decipher Ca2+ signals and initiate specific signaling processes, and thus controlling cellular functions. The physiological functions that rely on CaMKII are unsurprisingly diverse, ranging from regulating contractile state and cellular proliferation to Ca2+ homeostasis and cellular permeability. This review will focus on emerging evidence of CaMKII as an essential component of the vascular system, with a focus on the kinase isoform/splice variants and cellular system studied.

scholarly journals A Fresh Look at the Structure, Regulation, and Functions of Fodrin

2020 ◽  
Vol 40 (17) ◽  
Author(s):  
Jamuna S. Sreeja ◽  
Rince John ◽  
Dhrishya Dharmapal ◽  
Rohith Kumar Nellikka ◽  
Suparna Sengupta
Keyword(s):  
Posttranslational Modifications ◽  
Mammalian Cells ◽  
Structural Integrity ◽  
Cell Function ◽  
Cell Types ◽  
Erythroid Cell ◽  
Structural Variations ◽  
Neuronal Tissues ◽  
Different Cell Types ◽  
Neuronal Disorders

ABSTRACT Fodrin and its erythroid cell-specific isoform spectrin are actin-associated fibrous proteins that play crucial roles in the maintenance of structural integrity in mammalian cells, which is necessary for proper cell function. Normal cell morphology is altered in diseases such as various cancers and certain neuronal disorders. Fodrin and spectrin are two-chain (αβ) molecules that are encoded by paralogous genes and share many features but also demonstrate certain differences. Fodrin (in humans, typically a heterodimer of the products of the SPTAN1 and SPTBN1 genes) is expressed in nearly all cell types and is especially abundant in neuronal tissues, whereas spectrin (in humans, a heterodimer of the products of the SPTA1 and SPTB1 genes) is expressed almost exclusively in erythrocytes. To fulfill a role in such a variety of different cell types, it was anticipated that fodrin would need to be a more versatile scaffold than spectrin. Indeed, as summarized here, domains unique to fodrin and its regulation by Ca2+, calmodulin, and a variety of posttranslational modifications (PTMs) endow fodrin with additional specific functions. However, how fodrin structural variations and misregulated PTMs may contribute to the etiology of various cancers and neurodegenerative diseases needs to be further investigated.

scholarly journals SETD2 negatively regulates cell size through its catalytic activity and SRI domain

2021 ◽  
Author(s):  
Thom M Molenaar ◽  
Eliza Mari Kwesi-Maliepaard ◽  
Joana Silva ◽  
Muddassir Malik ◽  
William J Faller ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Rna Polymerase Ii ◽  
Cell Size ◽  
Cell Function ◽  
Size Control ◽  
Cell Types ◽  
Negative Regulator ◽  
Cellular Functions ◽  
Global Protein Synthesis

Cell size varies between cell types but is tightly regulated by cell-intrinsic and extrinsic mechanisms. Cell-size control is important for cell function and changes in cell size are frequently observed in cancer cells. Here we uncover a non-canonical role of SETD2 in regulating cell size. SETD2 is a lysine methyltransferase and a tumor suppressor protein involved in transcription regulation, RNA processing and DNA repair. At the molecular level, SETD2 is best known for associating with RNA polymerase II through its Set2-Rbp1 interacting (SRI) domain and methylating histone H3 on lysine 36 (H3K36) during transcription. Although most of the cellular functions of SETD2 have been linked to this activity, several non-histone substrates of SETD2 have recently been identified, some of which have been linked to novel functions of SETD2 beyond chromatin regulation. Using multiple, independent perturbation strategies we identify SETD2 as a negative regulator of global protein synthesis rates and cell size. We provide evidence that this function is dependent on the catalytic activity of SETD2 but independent of H3K36 methylation. Paradoxically, ectopic overexpression of a decoy SRI domain also increased cell size, suggesting that the relevant substrate is engaged by SETD2 via its SRI domain. These data add a central role of SETD2 in regulating cellular physiology and warrant further studies on separating the different functions of SETD2 in cancer development.

scholarly journals Physiological and Cellular Functions of Vitamin K on Cardiovascular Function

2021 ◽  
Author(s):  
Meneerah A. Aljafary ◽  
Hussah Alshwyeh ◽  
Nada Alahmadi ◽  
Adeeb Shehzad ◽  
Huseyin Tombuloglu ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Vitamin K ◽  
Vascular System ◽  
Vascular Endothelial Cells ◽  
Cell Types ◽  
Negative Influence ◽  
The Body ◽  
Dietary Vitamin ◽  
Primary Role ◽  
Cellular Functions

This chapter reviews the physiological and cellular functions of vitamin K in the cardiovascular system based on the latest pre-clinical and clinical evidence. Vitamin K belongs to a family of structurally similar fat-soluble vitamins, actively required by the body for the synthesis of essential proteins as well as regulate blood clotting, bone metabolism and calcium level. The authors emphasize the quintessential association between dietary vitamin K2 and cardiovascular diseases shown in various studies. The association, through the vitamin K - dependent hormones, plays a primary role in regulating calcification of different cell types, especially their role in calcification of the vascular endothelial cells. The consequences of vitamin K deficiency in the vascular system are unfavorable, shown in various clinical studies on statins - well-known inhibitors of vitamin K production in the body. New clinical insights suggest that vitamin K levels in the body and its dietary supplementation play a crucial role in cardiovascular disease prevention. There is negative influence of these antagonist’s pate in vascular composition and functions. Therefore, there is a need for prospective studies to make more in-depth exploration and increase the current understanding of this critical relationship to confidently apply such knowledge to prevent cardiovascular diseases and improve their outcomes.

scholarly journals Modulation of cellular redox homeostasis by the endocannabinoid system

Open Biology ◽  
2016 ◽  
Vol 6 (4) ◽  
pp. 150276 ◽  
Author(s):  
Christopher Lipina ◽  
Harinder S. Hundal
Keyword(s):  
Cross Talk ◽  
Cell Function ◽  
Redox Homeostasis ◽  
Endocannabinoid System ◽  
Cell Types ◽  
Cellular Functions ◽  
Cellular Redox ◽  
The Stability ◽  
Different Cell Types ◽  
Signalling Systems

The endocannabinoid system (ECS) and reactive oxygen species (ROS) constitute two key cellular signalling systems that participate in the modulation of diverse cellular functions. Importantly, growing evidence suggests that cross-talk between these two prominent signalling systems acts to modulate functionality of the ECS as well as redox homeostasis in different cell types. Herein, we review and discuss evidence pertaining to ECS-induced regulation of ROS generating and scavenging mechanisms, as well as highlighting emerging work that supports redox modulation of ECS function. Functionally, the studies outlined reveal that interactions between the ECS and ROS signalling systems can be both stimulatory and inhibitory in nature, depending on cell stimulus, the source of ROS species and cell context. Importantly, such cross-talk may act to maintain cell function, whereas abnormalities in either system may propagate and undermine the stability of both systems, thereby contributing to various pathologies associated with their dysregulation.

scholarly journals The Calcium/Calmodulin-Dependent Kinases II and IV as Therapeutic Targets in Neurodegenerative and Neuropsychiatric Disorders

2021 ◽  
Vol 22 (9) ◽  
pp. 4307
Author(s):  
Kinga Sałaciak ◽  
Aleksandra Koszałka ◽  
Elżbieta Żmudzka ◽  
Karolina Pytka
Keyword(s):  
Drug Design ◽  
Therapeutic Targets ◽  
Neuropsychiatric Disorders ◽  
Cellular Functions ◽  
Calcium Calmodulin Dependent ◽  
Regulatory Processes ◽  
Neuropsychiatric Diseases ◽  
Future Drug ◽  
Structure And Functions

CaMKII and CaMKIV are calcium/calmodulin-dependent kinases playing a rudimentary role in many regulatory processes in the organism. These kinases attract increasing interest due to their involvement primarily in memory and plasticity and various cellular functions. Although CaMKII and CaMKIV are mostly recognized as the important cogs in a memory machine, little is known about their effect on mood and role in neuropsychiatric diseases etiology. Here, we aimed to review the structure and functions of CaMKII and CaMKIV, as well as how these kinases modulate the animals’ behavior to promote antidepressant-like, anxiolytic-like, and procognitive effects. The review will help in the understanding of the roles of the above kinases in the selected neurodegenerative and neuropsychiatric disorders, and this knowledge can be used in future drug design.

scholarly journals Modulation of Vascular Cell Function by Bim Expression

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Margaret E. Morrison ◽  
Tammy L. Palenski ◽  
Nasim Jamali ◽  
Nader Sheibani ◽  
Christine M. Sorenson
Keyword(s):  
Endothelial Cells ◽  
Vascular Function ◽  
Cell Function ◽  
Unique Contribution ◽  
Cellular Functions ◽  
Vegf Expression ◽  
Vascular Cell ◽  
Proapoptotic Protein ◽  
Retinal Endothelial Cell ◽  
And Function

Apoptosis of vascular cells, including pericytes and endothelial cells, contributes to disease pathogenesis in which vascular rarefaction plays a central role. Bim is a proapoptotic protein that modulates not only apoptosis but also cellular functions such as migration and extracellular matrix (ECM) protein expression. Endothelial cells and pericytes each make a unique contribution to vascular formation and function although the details require further delineation. Here we set out to determine the cell autonomous impact of Bim expression on retinal endothelial cell and pericyte function using cells prepared from Bim deficient (Bim−/−) mice. Bim−/−endothelial cells displayed an increased production of ECM proteins, proliferation, migration, adhesion, and VEGF expression but, a decreased eNOS expression and nitric oxide production. In contrast, pericyte proliferation decreased in the absence of Bim while migration, adhesion, and VEGF expression were increased. In addition, we demonstrated that the coculturing of either wild-type or Bim−/−endothelial cells with Bim−/−pericytes diminished their capillary morphogenesis. Thus, our data further emphasizes the importance of vascular cell autonomous regulatory mechanisms in modulation of vascular function.

scholarly journals ­PlGF Regulates Angiopoietin-1 and Tie-2 Expression in Human Retinal Endothelial Cell-Pericyte Cocultures and iPSC-Derived Vascular Organoids through VEGFR1

2021 ◽  
Author(s):  
Hu Huang ◽  
Madhu Saddala ◽  
Rajiv Ravindra Mohan
Keyword(s):  
Cell Function ◽  
Cell Types ◽  
Experimental Models ◽  
Receptor Expression ◽  
Therapeutic Interventions ◽  
Dependent Manner ◽  
Sequencing Data ◽  
Vascular Cell ◽  
Diabetic Vasculopathy ◽  
Induced Pluripotent

Abstract Placental growth factor (PlGF) and Angiopoietin (Ang)-1 are two angiogenic factors that play vital roles in vascular cell growth and stabilization. The present study's objective is to examine PlGF's regulation of Ang-1 and its Tie-2 receptor expression in human vascular cells and vasculature. We exploited the cocultures of human primary retinal endothelial cells (HREC) and pericytes (HRP) and the blood vessel or vascular organoids derived from human-induced pluripotent stem cells (iPSC) as experimental models. In the HREC-HRP cocultures, PlGF blockage upregulated the expressions of Ang-1 and Tie-2 in an antibody dose-dependent manner. Upregulation of Ang-1 and Tie-2 by PlGF blockade did not occur in HREC and HRP monocultures but only in HREC-HRP cocultures, indicating the interactions of the two cell types. VEGFR1 inhibition diminished Ang-1 and Tie-2 upregulation caused by PlGF blockade and reduced pericyte variability in high glucose conditions. In the iPSC-derived vascular organoids (VO), PlGF, Ang-1, and Ang-2 were expressed mainly by perivascular cells. Bioinformatics analysis of RNA sequencing data revealed that diabetes-mimicking conditions upregulated PlGF and Ang-2 expressions in the VO cultures. PlGF blockade upregulated Ang-1 and Tie-2 expression and promoted pericyte coverage and association with ECs in the VO. Together, the data suggest that PlGF regulates Ang-1 and Tie-2 expression in part through VEGFR1, which is involved in vascular cell function and stabilization. The findings may help design new therapeutic interventions for diabetic vasculopathy, such as diabetic macular edema and proliferative diabetic retinopathy, by targeting PlGF and Ang signaling pathways.

Correlation Between Cellular Functions and Morphological Changes of Human Trophoblast in Vitro

1975 ◽  
Vol 33 ◽  
pp. 600-601
Author(s):  
John C. Garancis ◽  
Robert O. Hussa ◽  
Michael T. Story ◽  
Donald Yorde ◽  
Roland A. Pattillo
Keyword(s):  
Electron Microscopy ◽  
Cellular Proliferation ◽  
Morphological Changes ◽  
Culture Fluid ◽  
Cellular Functions ◽  
Human Trophoblast ◽  
Transmission Electron ◽  
Marked Activity ◽  
Malignant Trophoblast

Human malignant trophoblast cells in continuous culture were incubated for 3 days in medium containing 1 mM N6-O2'-dibutyryl cyclic adenosine 3':5'-monophosphate (dibutyryl cyclic AMP) and 1 mM theophylline. The culture fluid was replenished daily. Stimulated cultures secreted many times more chorionic gonadotropin and estrogens than did control cultures in the absence of increased cellular proliferation. Scanning electron microscopy revealed remarkable surface changes of stimulated cells. Control cells (not stimulated) were smooth or provided with varying numbers of microvilli (Fig. 1). The latter, usually, were short and thin. The surface features of stimulated cells were considerably different. There was marked increase of microvilli which appeared elongated and thick. Many cells were covered with confluent polypoid projections (Fig. 2). Transmission electron microscopy demonstrated marked activity of cytoplasmic organelles. Mitochondria were increased in number and size; some giant forms with numerous cristae were observed.

Freeze-substitution of rye grass and ragweed pollen grains

1990 ◽  
Vol 48 (3) ◽  
pp. 686-687
Author(s):  
Liza B. Martinez ◽  
Susan M. Wick
Keyword(s):  
Cell Function ◽  
Pollen Grains ◽  
Freeze Substitution ◽  
Cell Types ◽  
Rapid Freezing ◽  
Rye Grass ◽  
Acrylic Resins ◽  
Allergenic Proteins ◽  
Cold Embedding ◽  
Structural Preservation

Rapid freezing and freeze-substitution have been employed as alternatives to chemical fixation because of the improved structural preservation obtained in various cell types. This has been attributed to biomolecular immobilization derived from the extremely rapid arrest of cell function. These methods allow the elimination of conventionally used fixatives, which may have denaturing or “masking” effects on proteins. Thus, this makes them ideal techniques for immunocytochemistry, in which preservation of both ultrastructure and antigenicity are important. These procedures are also compatible with cold embedding acrylic resins which are known to increase sensitivity in immunolabelling.This study reveals how rapid freezing and freeze-substitution may prove to be useful in the study of the mobile allergenic proteins of rye grass and ragweed. Most studies have relied on the use of osmium tetroxide to achieve the necessary ultrastructural detail in pollen whereas those that omitted it have had to contend with poor overall preservation.

scholarly journals Multiple Roles for Cholinergic Signaling from the Perspective of Stem Cell Function

2021 ◽  
Vol 22 (2) ◽  
pp. 666
Author(s):  
Toshio Takahashi
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Function ◽  
Cell Activity ◽  
Embryonic Stem ◽  
Cholinergic Neurons ◽  
Cell Types ◽  
Proliferative Potential ◽  
True Nature ◽  
Cholinergic Signaling

Stem cells have extensive proliferative potential and the ability to differentiate into one or more mature cell types. The mechanisms by which stem cells accomplish self-renewal provide fundamental insight into the origin and design of multicellular organisms. These pathways allow the repair of damage and extend organismal life beyond that of component cells, and they probably preceded the evolution of complex metazoans. Understanding the true nature of stem cells can only come from discovering how they are regulated. The concept that stem cells are controlled by particular microenvironments, also known as niches, has been widely accepted. Technical advances now allow characterization of the zones that maintain and control stem cell activity in several organs, including the brain, skin, and gut. Cholinergic neurons release acetylcholine (ACh) that mediates chemical transmission via ACh receptors such as nicotinic and muscarinic receptors. Although the cholinergic system is composed of organized nerve cells, the system is also involved in mammalian non-neuronal cells, including stem cells, embryonic stem cells, epithelial cells, and endothelial cells. Thus, cholinergic signaling plays a pivotal role in controlling their behaviors. Studies regarding this signal are beginning to unify our understanding of stem cell regulation at the cellular and molecular levels, and they are expected to advance efforts to control stem cells therapeutically. The present article reviews recent findings about cholinergic signaling that is essential to control stem cell function in a cholinergic niche.

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