Calcium Desensitization Mechanism and Treatment for Vascular Hyporesponsiveness After Shock

2016 ◽  
pp. 119-136
Author(s):  
Liangming Liu ◽  
Tao Li ◽  
Guangming Yang ◽  
Chenyang Duan
Keyword(s):  
Calcium Desensitization

scholarly journals Gene-Targeted Mice with the Human Troponin T R141W Mutation Develop Dilated Cardiomyopathy with Calcium Desensitization

PLoS ONE ◽  
2016 ◽  
Vol 11 (12) ◽  
pp. e0167681 ◽  
Author(s):  
Mohun Ramratnam ◽  
Guy Salama ◽  
Ravi K. Sharma ◽  
David Wen Rui Wang ◽  
Stephen H. Smith ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Troponin T ◽  
Calcium Desensitization

scholarly journals Dual oxidase2 is expressed all along the digestive tract

2005 ◽  
Vol 288 (5) ◽  
pp. G933-G942 ◽  
Author(s):  
Rabii Ameziane El Hassani ◽  
Nesrine Benfares ◽  
Bernard Caillou ◽  
Monique Talbot ◽  
Jean-Christophe Sabourin ◽  
...  
Keyword(s):  
Digestive Tract ◽  
Critical Role ◽  
Human Colon ◽  
Rat Colon ◽  
Differentiated Cells ◽  
Calcium Desensitization ◽  
Dual Oxidase ◽  
Rectal Glands ◽  
Immunohistochemical Studies

The dual oxidase (Duox)2 flavoprotein is strongly expressed in the thyroid gland, where it plays a critical role in the synthesis of thyroid hormones by providing thyroperoxidase with H2O2. DUOX2 mRNA was recently detected by RT-PCR and in-situ hybridization experiments in other tissues, such as rat colon and rat and human epithelial cells from the salivary excretory ducts and rectal glands. We examined Duox2 expression at the protein level throughout the porcine digestive tract and in human colon. Western blot analysis identified Duox2 as the same two molecular species ( Mr 165 and 175 kDa) as detected in the thyroid. It was expressed in all the tissues tested, but the highest levels were found in the cecum and sigmoidal colon. Immunohistochemical studies showed that Duox2 protein is mainly present in these parts of the gut and located at the apical membrane of the enterocytes in the brush border, indicating that it is expressed only in highly differentiated cells. A Ca2+/NADPH-dependent H2O2-generating system was associated with Duox2 protein expression, which had the same biochemical characteristics as the NADPH oxidase in the thyroid. Indeed, treatment of the thyroid and cecum particulate fractions with phenylarsine oxide resulted in complete calcium desensitization of both enzymes. A marked increase in DUOX2 expression was also found during spontaneous differentiation of postconfluent Caco-2 cells. The discovery of Duox2 as a novel source of H2O2 in the digestive tract, particularly in the cecum and colon, makes it a new candidate mediator of physiopathological processes.

scholarly journals Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest

Critical Care ◽  
2013 ◽  
Vol 17 (5) ◽  
pp. R245 ◽  
Author(s):  
Alessio Rungatscher ◽  
Seth Hallström ◽  
Alice Giacomazzi ◽  
Daniele Linardi ◽  
Elisabetta Milani ◽  
...  
Keyword(s):  
Myocardial Dysfunction ◽  
Circulatory Arrest ◽  
Deep Hypothermic Circulatory Arrest ◽  
Hypothermic Circulatory Arrest ◽  
Calcium Desensitization

Mesenteric Lymph Return Is an Important Contributor to Vascular Hyporeactivity and Calcium Desensitization After Hemorrhagic Shock

Shock ◽  
2012 ◽  
Vol 38 (2) ◽  
pp. 186-195 ◽  
Author(s):  
Zi-Gang Zhao ◽  
Chun-Yu Niu ◽  
Yan-Ling Wei ◽  
Yu-Ping Zhang ◽  
Yong-Hua Si ◽  
...  
Keyword(s):  
Hemorrhagic Shock ◽  
Important Contributor ◽  
Mesenteric Lymph ◽  
Calcium Desensitization ◽  
Vascular Hyporeactivity

scholarly journals Calcium desensitization in cardiac troponin C: a novel role in mouse skeletal muscle

2019 ◽  
Vol 597 (5) ◽  
pp. 1227-1229
Author(s):  
Matthew J. Novello ◽  
MengQi Zhang ◽  
Hannah E. Snyder ◽  
Qi‐Tong Lin
Keyword(s):  
Skeletal Muscle ◽  
Cardiac Troponin ◽  
Troponin C ◽  
Mouse Skeletal Muscle ◽  
Cardiac Troponin C ◽  
Calcium Desensitization

Cgmp-Dependent Calcium Desensitization Contributes to Vasodilator Response to Nitric Oxide in Rat Middle Cerebral Arteries

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 719-719
Author(s):  
Cheng-wen Sun ◽  
David R Harder ◽  
Richard J Roman
Keyword(s):  
Nitric Oxide ◽  
Guanylyl Cyclase ◽  
Cerebral Arteries ◽  
No Donor ◽  
Vasodilator Response ◽  
Calcium Desensitization ◽  
Vasoconstrictor Response ◽  
Middle Cerebral Arteries ◽  
Dependent Component ◽  
Dependent Mechanism

P142 We have recently reported that a cGMP-dependent mechanism as well as a cGMP-independent activation of K Ca channels secondary to a fall in 20-HETE contributes to the vasodilator response to NO in the cerebral circulation. The present study examines the mechanism for the cGMP-dependent component of the vasodilator response to NO in rat middle cerebral arteries (MCA). Administration of a NO donor, dose-dependently, increased the diameter of serotonin preconstricted MCA to 69.3±5.8% of control (n=6). 8-Br-cGMP (10 -8 to 10 -4 M) mimicked the effect of NO and increased the diameter of MCA to 58.7±3.6% of control (n=6). Blockade of K Ca channels with IBTX (10 -7 M, n=6) or depolarization with a 80 mM K + media (n=6)reduced the vasodilator response of MCA to NO by 70±6%, but they had little effect on the vasodilator response to 8-Br-cGMP. This suggests that activation of K + channels contribute to the vasodilator response to NO in MCA, but not the response to 8-Br-cGMP. We therefore examined the effects of NO and cGMP on Ca 2+ -induced contraction of rat MCAs permeablized with α-toxin (10 μg/ml) and ionomycin (10 μM). Elevations in bath Ca 2+ , from 10 -8 to 10 -5 M, decreased the diameter of these vessels by 60.9±3.7%. A NO donor, DEA-NONOate (10 -6 M, n=6)and 8-Br-cGMP (10 -4 M, n=6) both attenuated the vasoconstrictor response to elevations in bath Ca 2+ by 60%. Inhibition of guanylyl cyclase with ODQ (10 -5 M) prevented the effects of the NO donor, but not 8-Br-cGMP. These results indicate that the cGMP, PKG-dependent component of the vasodilator response of NO in rat MCA is mediated by desensitization of the contractile mechanism to calcium rather than activation of K + channels.

Inositol 1, 4, 5-trisphosphate-induced calcium mobilization is localized in Xenopus oocytes

1989 ◽  
Vol 238 (1292) ◽  
pp. 235-243 ◽  
Keyword(s):  
Xenopus Oocytes ◽  
Calcium Mobilization ◽  
Calcium Oscillations ◽  
Chloride Conductance ◽  
Calcium Transients ◽  
Animal Pole ◽  
Induced Membrane ◽  
Inositol 1 ◽  
Calcium Desensitization ◽  
Neighbouring Region

Injection of inositol 1, 4, 5-trisphosphate (Ins(1, 4, 5) P 3 ) into the animal pole of Xenopus oocytes induced membrane depolarization due to the internal mobilization of calcium, which activates a chloride conductance. Repetitive injections of Ins(1, 4, 5) P 3 results in desensitization probably as a result of depletion of the internal store of calcium. Desensitization was restricted to the region surrounding the site of injection. Injection of Ins(1, 4, 5) P 3 at one position induced desensitization, which failed to spread to a neighbouring region ( ca . 200 μm away). Even when sufficient Ins(1, 4, 5) P 3 was injected to induce calcium oscillations, there was still no evidence for the effects of Ins(1, 4, 5) P 3 spreading to neighbouring regions. The fact that periodic calcium transients could also be established by the repetitive injection of small amounts of Ins(1, 4, 5) P 3 suggests that calcium oscillations may also be localized. It is concluded that the Ins(1, 4, 5) P 3 -sensitive store of calcium comprises separate local compartments that can be activated independently of each other.

scholarly journals Myofilament Glycation in Diabetes Reduces Contractility by Inhibiting Tropomyosin Movement, is Rescued by cMyBPC Domains

2021 ◽  
Author(s):  
Maria Papadaki ◽  
Theerachat Kampaengsri ◽  
Samantha K Barrick ◽  
Stuart A. Campbell ◽  
Samantha P Harris ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Calcium Sensitivity ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Developing Heart ◽  
Calcium Desensitization ◽  
Promising Therapeutic Target ◽  
Patients With Diabetes ◽  
Experimental Findings

Diabetes doubles the risk of developing heart failure (HF). As the prevalence of diabetes grows, so will HF unless the mechanisms connecting these diseases can be identified. Methylglyoxal (MG) is a glycolysis by-product that forms irreversible modifications on lysine and arginine, called glycation. We previously found that myofilament MG glycation causes sarcomere contractile dysfunction and is increased in patients with diabetes and HF. The aim of this study was to discover the molecular mechanisms by which MG glycation of myofilament proteins cause sarcomere dysfunction and to identify therapeutic avenues to compensate. In humans with type 2 diabetes without HF, we found increased glycation of sarcomeric actin compared to non-diabetics and it correlated with decreased calcium sensitivity. Depressed calcium sensitivity is pathogenic for HF, therefore myofilament glycation represents a promising therapeutic target to inhibit the development of HF in diabetics. To identify possible therapeutic targets, we further defined the molecular actions of myofilament glycation. Skinned myocytes exposed to 100 uM MG exhibited decreased calcium sensitivity, maximal calcium-activated force, and crossbridge kinetics. Replicating MG's functional affects using a computer simulation of sarcomere function predicted simultaneous decreases in tropomyosin's blocked-to-closed rate transition and crossbridge duty cycle were consistent with all experimental findings. Stopped-flow experiments and ATPase activity confirmed MG decreased the blocked-to-closed transition rate. Currently, no therapeutics target tropomyosin, so as proof-of-principal, we used a n-terminal peptide of myosin-binding protein C, previously shown to alter tropomyosin's position on actin. C0C2 completely rescued MG-induced calcium desensitization, suggesting a possible treatment for diabetic HF.

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