scholarly journals Altered Expression and Function of Ryanodine Receptors and FKBP12.6 after Subarachnoid Hemorrhage: More than Meets the Eye

2010 ◽  
Vol 31 (1) ◽  
pp. 1-2 ◽  
Author(s):  
William F Jackson
Keyword(s):  
Smooth Muscle ◽  
Subarachnoid Hemorrhage ◽  
Ryanodine Receptors ◽  
Feedback Regulation ◽  
Negative Feedback Regulation ◽  
Altered Expression ◽  
Fk506 Binding Protein ◽  
Cerebrovascular Smooth Muscle Cells ◽  
And Function ◽  
Related Proteins

Subarachnoid hemorrhage decreases the expression of ryanodine receptors and increases the expression of the immunophilin, FK506-binding protein (FKBP)12.6 in cerebrovascular smooth muscle cells, reducing the occurrence of Ca2+ sparks, limiting negative feedback regulation of cerebrovascular tone and promoting vasospasm. However, given the large number of binding partners with which FKBP12.6 and related proteins interact, it appears likely that the altered expression of this immunophilin will have a broader impact on cerebrovascular smooth muscle function. In addition, the mechanisms responsible for the measured changes in expression of ryanodine receptors and FKBP12.6 yet remain unknown. These topics should prove to be fertile ground for future studies.

scholarly journals Chaperones and Proteostasis: Role in Parkinson’s Disease

Diseases ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 24 ◽  
Author(s):  
Neha Joshi ◽  
Atchaya Raveendran ◽  
Shirisha Nagotu
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Three Dimensional ◽  
Cellular Protein ◽  
The Body ◽  
Dimensional Structure ◽  
Protein Homeostasis ◽  
Altered Expression ◽  
And Function ◽  
Related Proteins

Proper folding to attain a defined three-dimensional structure is a prerequisite for the functionality of a protein. Improper folding that eventually leads to formation of protein aggregates is a hallmark of several neurodegenerative disorders. Loss of protein homeostasis triggered by cellular stress conditions is a major contributing factor for the formation of these toxic aggregates. A conserved class of proteins called chaperones and co-chaperones is implicated in maintaining the cellular protein homeostasis. Expanding the body of evidence highlights the role of chaperones as central mediators in the formation, de-aggregation and degradation of the aggregates. Altered expression and function of chaperones is associated with many neurodegenerative diseases including Parkinson’s disease. Several studies indicate that chaperones are at the center of the cause and effect cycle of this disease. An overview of the various chaperones that are associated with homeostasis of Parkinson’s disease-related proteins and their role in pathogenicity will be discussed in this review.

Modulation of type-1 Ins(1,4,5)P3 receptor channels by the FK506-binding protein, FKBP12

2002 ◽  
Vol 361 (2) ◽  
pp. 401-407 ◽  
Author(s):  
Sheila L. DARGAN ◽  
Edward J. A. LEA ◽  
Alan P. DAWSON
Keyword(s):  
Lipid Bilayers ◽  
Calcium Release ◽  
Single Channel ◽  
Binding Protein ◽  
Ryanodine Receptors ◽  
Fk506 Binding Protein ◽  
Single Channel Activity ◽  
And Function ◽  
First Time

FK506-binding protein (FKBP12) is highly expressed in neuronal tissue, where it is proposed to localize calcineurin to intracellular calcium-release channels, ryanodine receptors and Ins(1,4,5)P3 receptors (InsP3Rs). The effects of FKBP12 on ryanodine receptors have been well characterized but the nature and function of binding of FKBP12 to InsP3R is more controversial, with evidence for and against a tight interaction between these two proteins. To investigate this, we incorporated purified type-1 InsP3R from rat cerebellum into planar lipid bilayers to monitor the effects of exogenous recombinant FKBP12 on single-channel activity, using K+ as the current carrier. Here we report for the first time that FKBP12 causes a substantial change in single-channel properties of the type-1 InsP3R, specifically to increase the amount of time the channel spends in a fully open state. In the presence of ATP, FKBP12 can also induce co-ordinated gating with neighbouring receptors. The effects of FKBP12 were reversed by FK506. We also present data showing that rapamycin, at sub-optimal concentrations of Ins(2,4,5)P3, decreases the rate of calcium release from cerebellar microsomes. These results provide evidence for a direct functional interaction between FKBP12 and the type-1 InsP3R.

scholarly journals Cytoglobin overexpression facilitates proliferation and migration of vascular smooth muscle cells

2020 ◽  
Vol 72 (2) ◽  
pp. 165-172 ◽  
Author(s):  
Lei Li ◽  
Yilin Xie ◽  
Shen Li ◽  
Juanjuan Tan ◽  
Yingchun Qin ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Feedback Regulation ◽  
Muscle Cells ◽  
Nuclear Antigen ◽  
Matrix Remodeling ◽  
Negative Feedback Regulation ◽  
Vsmc Proliferation

Cytoglobin, a recently discovered globin, is expressed in vascular smooth muscle cells (VSMCs). Loss of cytoglobin provides a protective effect on vascular reconstruction but the effect of its overexpression is unclear. The aim of the study was to investigate the effect of cytoglobin overexpression on the migration and proliferation of VSMCs and possible mechanisms. We detected the expression of cytoglobin in hypertensive and normotensive rat aortas, with negative feedback regulation between cytoglobin and hypertension observed. The expression of cytoglobin was significantly decreased in hypertensive rats compared to normotensive rats, but VSMCs overexpressing cytoglobin displayed increased cell migration and proliferation, which led to a phenotypic switch. The increased expression of matrix metalloproteinase 9 and collagen Ia suggests a role for cytoglobin in extracellular matrix remodeling. Increased expression of proliferating cell nuclear antigen and decreased expression of p27 implies that cytoglobin is involved in modulating VSMC proliferation. Our findings indicate that cytoglobin may play an important role in vascular wall remodeling.

Plasticity of Cerebrovascular Smooth Muscle Cells After Subarachnoid Hemorrhage

2014 ◽  
Vol 5 (3) ◽  
pp. 365-376 ◽  
Author(s):  
Lars Edvinsson ◽  
Stine Schmidt Larsen ◽  
Aida Maddahi ◽  
Janne Nielsen
Keyword(s):  
Smooth Muscle ◽  
Subarachnoid Hemorrhage ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cerebrovascular Smooth Muscle Cells

scholarly journals SOCS Proteins in Immunity, Inflammatory Diseases, and Immune-Related Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Mohamed Luban Sobah ◽  
Clifford Liongue ◽  
Alister C. Ward
Keyword(s):  
Immune Cell ◽  
Inflammatory Diseases ◽  
Feedback Regulation ◽  
Cytokine Signaling ◽  
Negative Feedback Regulation ◽  
Autoimmune Conditions ◽  
Socs Proteins ◽  
Ifn Γ ◽  
And Function ◽  
Immune Defects

Cytokine signaling represents one of the cornerstones of the immune system, mediating the complex responses required to facilitate appropriate immune cell development and function that supports robust immunity. It is crucial that these signals be tightly regulated, with dysregulation underpinning immune defects, including excessive inflammation, as well as contributing to various immune-related malignancies. A specialized family of proteins called suppressors of cytokine signaling (SOCS) participate in negative feedback regulation of cytokine signaling, ensuring it is appropriately restrained. The eight SOCS proteins identified regulate cytokine and other signaling pathways in unique ways. SOCS1–3 and CISH are most closely involved in the regulation of immune-related signaling, influencing processes such polarization of lymphocytes and the activation of myeloid cells by controlling signaling downstream of essential cytokines such as IL-4, IL-6, and IFN-γ. SOCS protein perturbation disrupts these processes resulting in the development of inflammatory and autoimmune conditions as well as malignancies. As a consequence, SOCS proteins are garnering increased interest as a unique avenue to treat these disorders.

A functional polymorphism of FK506-binding protein 51 (FKBP5) gene affects personality traits of harm avoidance and cooperativeness in healthy subjects

2011 ◽  
Vol 26 (S2) ◽  
pp. 815-815
Author(s):  
N. Shibuya ◽  
A. Suzuki ◽  
R. Sadahiro ◽  
M. Kamata ◽  
Y. Matsumoto ◽  
...  
Keyword(s):  
Personality Traits ◽  
Hpa Axis ◽  
Negative Feedback ◽  
Healthy Subjects ◽  
Binding Protein ◽  
Feedback Regulation ◽  
Harm Avoidance ◽  
Stress Tests ◽  
Negative Feedback Regulation ◽  
Fk506 Binding Protein

AimsPrevious studies have shown that the function of hypothalamic-pituitary-adrenal (HPA) axis is involved in the characterization of personality traits. FK506-binding protein 51 (FKBP51 or FKBP5) is a co-chaperone of heat-shock protein 90, and plays an important role in the negative feedback regulation of HPA axis function. It has been reported that a C/T single nucleotide polymorphism in the intron 2 of FKBP5 gene (rs1360780) affects FKBP5 protein levels and cortisol response to dexamethasone and psychological stress tests. Therefore, it is hypothesized that the FKBP5 polymorphism affects personality traits. In the present study, we studied the association between this polymorphism and personality traits in healthy subjects.MethodsSubjects were 826 Japanese healthy volunteers. Personality traits were assessed by the Temperament and Character Inventory (TCI), and the FKBP5 genotype was detected by a real-time PCR and cycling probe technology for SNP typing.ResultsIn total subjects, the group with the T allele predictive of impaired negative feedback regulation of the HPA axis had higher scores of harm avoidance (p = 0.043) and lower scores of cooperativeness (p = 0.019) compared to that without the T allele. The T allele was associated with higher scores of harm avoidance in females (p = 0.020) and lower scores of cooperativeness in males (p = 0.015).ConclusionThe present study thus suggests that the FKBP5 polymorphism affects harm avoidance and cooperativeness in healthy subjects, with gender specificity.

PW180 Expression and Function of Ryanodine Receptors in Mesenteric Artery Smooth Muscle Cells from patients with hypertension

Global Heart ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e294
Author(s):  
Pengyun Li ◽  
liang mao ◽  
jun cheng ◽  
jing wen ◽  
yan yang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Mesenteric Artery ◽  
Ryanodine Receptors ◽  
Muscle Cells ◽  
And Function
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