Omega-3 fatty acids and atorvastatin affect connexin 43 expression in the aorta of hereditary hypertriglyceridemic ratsThis article is one of a selection of papers published in a special issue on Advances in Cardiovascular Research.

2009 ◽  
Vol 87 (12) ◽  
pp. 1074-1082 ◽  
Author(s):  
Katarína Dlugošová ◽  
Peter Weismann ◽  
Iveta Bernátová ◽  
Ružena Sotníková ◽  
Ján Slezák ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Connexin 43 ◽  
Structural Integrity ◽  
Disease Incidence ◽  
Omega 3 ◽  
Cardiovascular Research ◽  
Cx43 Expression ◽  
Junction Protein ◽  
Effect Of Treatment ◽  
Gap Junction Protein

Statins and omega-3 polyunsaturated fatty acids (n-3 PUFA) reduce cardiovascular disease incidence during hypertriglyceridemia (HTG). To elucidate possible cardioprotective mechanisms, we focused on gap junction protein connexin 43 (Cx43). Its expression is disturbed during atherogenesis, but little information is available on its expression during HTG. Experiments were performed on adult male hereditary HTG (hHTG) rats treated with n-3 PUFA (30 mg/day) and atorvastatin (0.5 mg/100 g body weight per day) for 2 months. Cx43 expression and distribution in the aorta were investigated by using Western blotting and immunolabeling, followed by quantitative analysis. Transmission electronmicroscopy was used to study ultrastructure of endothelial contact sites. In contrast to age-matched Wistar, Cx43 expression in aorta of hHTG rats was significantly higher (p < 0.05), and prominent Cx43 immunospots were seen in tunica media and less in endothelium of hHTG rats. Changes in Cx43 expression were accompanied by local qualitative subcellular alterations of interendothelial connections. Treatment of hHTG rats with n-3 PUFA and atorvastatin markedly lowered Cx43 expression in aorta and modified connexin distribution in endothelium and media (p < 0.05 vs. untreated hHTG). The protective effect of treatment of HTG was observed on the structural integrity of the endothelium and was readily visible at the molecular level. Results indicate the involvement of altered Cx43 expression in vascular pathophysiology during HTG and during HTG treatment.

scholarly journals Amyloid-β regulates gap junction protein connexin 43 trafficking in cultured primary astrocytes

2020 ◽  
Vol 295 (44) ◽  
pp. 15097-15111
Author(s):  
Mahua Maulik ◽  
Lakshmy Vasan ◽  
Abhishek Bose ◽  
Saikat Dutta Chowdhury ◽  
Neelanjana Sengupta ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Connexin 43 ◽  
Cx43 Expression ◽  
Chemical Chaperone ◽  
Junction Protein ◽  
Gap Junction Coupling ◽  
Gap Junction Protein ◽  
Junction Coupling ◽  
And Function

Altered expression and function of astroglial gap junction protein connexin 43 (Cx43) has increasingly been associated to neurotoxicity in Alzheimer disease (AD). Although earlier studies have examined the effect of increased β-amyloid (Aβ) on Cx43 expression and function leading to neuronal damage, underlying mechanisms by which Aβ modulates Cx43 in astrocytes remain elusive. Here, using mouse primary astrocyte cultures, we have examined the cellular processes by which Aβ can alter Cx43 gap junctions. We show that Aβ25-35 impairs functional gap junction coupling yet increases hemichannel activity. Interestingly, Aβ25-35 increased the intracellular pool of Cx43 with a parallel decrease in gap junction assembly at the surface. Intracellular Cx43 was found to be partly retained in the endoplasmic reticulum-associated cell compartments. However, forward trafficking of the newly synthesized Cx43 that already reached the Golgi was not affected in Aβ25-35-exposed astrocytes. Supporting this, treatment with 4-phenylbutyrate, a well-known chemical chaperone that improves trafficking of several transmembrane proteins, restored Aβ-induced impaired gap junction coupling between astrocytes. We further show that interruption of Cx43 endocytosis in Aβ25-35-exposed astrocytes resulted in their retention at the cell surface in the form of functional gap junctions indicating that Aβ25-35 causes rapid internalization of Cx43 gap junctions. Additionally, in silico molecular docking suggests that Aβ can bind favorably to Cx43. Our study thus provides novel insights into the cellular mechanisms by which Aβ modulates Cx43 function in astrocytes, the basic understanding of which is vital for the development of alternative therapeutic strategy targeting connexin channels in AD.

scholarly journals Hindlimb unloading results in increased predisposition to cardiac arrhythmias and alters left ventricular connexin 43 expression

2013 ◽  
Vol 304 (5) ◽  
pp. R362-R373 ◽  
Author(s):  
Julia A. Moffitt ◽  
Matthew K. Henry ◽  
Kathryn C. Welliver ◽  
Amanda J. Jepson ◽  
Emily R. Garnett
Keyword(s):  
Cardiac Arrhythmias ◽  
Connexin 43 ◽  
Electrical Coupling ◽  
Left Ventricular ◽  
Hindlimb Unloading ◽  
Cx43 Expression ◽  
Cardiovascular Deconditioning ◽  
Junction Protein ◽  
Gap Junction Protein ◽  
Sympathovagal Imbalance

Hindlimb unloading (HU) is a well-established animal model of cardiovascular deconditioning. Previous data indicate that HU results in cardiac sympathovagal imbalance. It is well established that cardiac sympathovagal imbalance increases the risk for developing cardiac arrhythmias. The cardiac gap junction protein connexin 43 (Cx43) is predominately expressed in the left ventricle (LV) and ensures efficient cell-to-cell electrical coupling. In the current study we wanted to test the hypothesis that HU would result in increased predisposition to cardiac arrhythmias and alter the expression and/or phosphorylation of LV-Cx43. Electrocardiographic data using implantable telemetry were obtained over a 10- to 14-day HU or casted control (CC) condition and in response to a sympathetic stressor using isoproterenol administration and brief restraint. The arrhythmic burden was calculated using a modified scoring system to quantify spontaneous and provoked arrhythmias. In addition, Western blot analysis was used to measure LV-Cx43 expression in lysates probed with antibodies directed against the total and an unphosphorylated form of Cx43 in CC and HU rats. HU resulted in a significantly greater total arrhythmic burden during the sympathetic stressor with significantly more ventricular arrhythmias occurring. In addition, there was increased expression of total LV-Cx43 observed with no difference in the expression of unphosphorylated LV-Cx43. Specifically, the increased expression of LV-Cx43 was consistent with the phosphorylated form. These data taken together indicate that cardiovascular deconditioning produced through HU results in increased predisposition to cardiac arrhythmias and increased expression of phosphorylated LV-Cx43.

scholarly journals Omega-3 PUFAs Suppress IL-1β-Induced Hyperactivity of Immunoproteasomes in Astrocytes

2021 ◽  
Vol 22 (11) ◽  
pp. 5410
Author(s):  
Emilia Zgorzynska ◽  
Barbara Dziedzic ◽  
Monika Markiewicz ◽  
Anna Walczewska
Keyword(s):  
Connexin 43 ◽  
Regulatory Element ◽  
Dependent Manner ◽  
Omega 3 ◽  
Junction Protein ◽  
Proteasome Subunits ◽  
Gap Junction Protein ◽  
Dose Dependent ◽  
The Brain

The role of immunoproteasome (iP) in astroglia, the cellular component of innate immunity, has not been clarified. The results so far indicate that neuroinflammation, a prominent hallmark of Alzheimer’s disease, strongly activates the iP subunits expression. Since omega-3 PUFAs possess anti-inflammatory and pro-resolving activity in the brain, we investigated the effect of DHA and EPA on the gene expression of constitutive (β1 and β5) and inducible (iβ1/LMP2 and iβ5/LMP7) proteasome subunits and proteasomal activity in IL-1β-stimulated astrocytes. We found that both PUFAs downregulated the expression of IL-1β-induced the iP subunits, but not the constitutive proteasome subunits. The chymotrypsin-like activity was inhibited in a dose-dependent manner by DHA, and much strongly in the lower concentration by EPA. Furthermore, we established that C/EBPα and C/EBPβ transcription factors, being the cis-regulatory element of the transcription complex, frequently activated by inflammatory mediators, participate in a reduction in the iP subunits’ expression. Moreover, the expression of connexin 43 the major gap junction protein in astrocytes, negatively regulated by IL-1β was markedly increased in PUFA-treated cells. These findings indicate that omega-3 PUFAs attenuate inflammation-induced hyperactivity of iPs in astrocytes and have a beneficial effect on preservation of interastrocytic communication by gap junctions.

scholarly journals Omega-3 Fatty Acids Reduce Lipopolysaccharide-Induced Abnormalities in Expression of Connexin-40 in Aorta of Hereditary Hypertriglyceridemic Rats

2016 ◽  
pp. S65-S76 ◽  
Author(s):  
K. FRIMMEL ◽  
R. SOTNÍKOVÁ ◽  
J. NAVAROVÁ ◽  
I. BERNÁTOVÁ ◽  
J. KRIŽÁK ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Single Dose ◽  
Gap Junction ◽  
Vascular Wall ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Junction Protein ◽  
Gap Junction Protein ◽  
Induced Changes ◽  
Endothelium Dependent Relaxation

Omega-3 fatty acids (Ω3FA) are known to reduce hypertriglyceridemia- and inflammation-induced vascular wall diseases. However, mechanisms of their effects are not completely clear. We examined, whether 10-day Ω3FA diet can reduce bacterial lipopolysaccharide-induced changes in expression of gap junction protein connexin40 (Cx40) in the aorta of hereditary hypertriglyceridemic (hHTG) rats. After administration of a single dose of lipopolysaccharide (LPS, 1 mg/kg, i.p.) to adult hHTG rats, animals were fed with Ω3FA diet (30 mg/kg/day) for 10 days. LPS decreased Cx40 expression that was associated with reduced acetylcholine-induced relaxation of aorta. Ω3FA administration to LPS rats had partial anti-inflammatory effects, associated with increased Cx40 expression and improved endothelium dependent relaxation of the aorta. Our results suggest that 10-day Ω3FA diet could protect endothelium-dependent relaxation of the aorta of hHTG rats against LPS-induced damage through the modulation of endothelial Cx40 expression.

Phosphorylation of connexin 43 induced by traumatic brain injury promotes exosome release

2018 ◽  
Vol 119 (1) ◽  
pp. 305-311 ◽  
Author(s):  
Wei Chen ◽  
Yijun Guo ◽  
Wenjin Yang ◽  
Lei Chen ◽  
Dabin Ren ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Gap Junction ◽  
Connexin 43 ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Cx43 Expression ◽  
Term Potentiation ◽  
Junction Protein

Traumatic brain injury (TBI) caused by the external force leads to the neuronal dysfunction and even death. TBI has been reported to significantly increase the phosphorylation of glial gap junction protein connexin 43 (Cx43), which in turn propagates damages into surrounding brain tissues. However, the neuroprotective and anti-apoptosis effects of glia-derived exosomes have also been implicated in recent studies. Therefore, we detected whether TBI-induced phosphorylation of Cx43 would promote exosome release in rat brain. To generate TBI model, adult male Sprague-Dawley rats were subjected to lateral fluid percussion injury. Phosphorylated Cx43 protein levels and exosome activities were quantified using Western blot analysis following TBI. Long-term potentiation (LTP) was also tested in rat hippocampal slices. TBI significantly increased the phosphorylated Cx43 and exosome markers expression in rat ipsilateral hippocampus, but not cortex. Blocking the activity of Cx43 or ERK, but not JNK, significantly suppressed TBI-induced exosome release in hippocampus. Furthermore, TBI significantly inhibited the induction of LTP in hippocampal slices, which could be partially but significantly restored by pretreatment with exosomes. The results imply that TBI-activated Cx43 could mediate a nociceptive effect by propagating the brain damages, as well as a neuroprotective effect by promoting exosome release. NEW & NOTEWORTHY We have demonstrated in rat traumatic brain injury (TBI) models that both phosphorylated connexin 43 (p-Cx43) expression and exosome release were elevated in the hippocampus following TBI. The promoted exosome release depends on the phosphorylation of Cx43 and requires ERK signaling activation. Exosome treatment could partially restore the attenuated long-term potentiation. Our results provide new insight for future therapeutic direction on the functional recovery of TBI by promoting p-Cx43-dependent exosome release but limiting the gap junction-mediated bystander effect.

Subcellular localization of the Na+/H+ exchanger NHE1 in rat myocardium

1999 ◽  
Vol 276 (2) ◽  
pp. H709-H717 ◽  
Author(s):  
Kevin Petrecca ◽  
Roxana Atanasiu ◽  
Sergio Grinstein ◽  
John Orlowski ◽  
Alvin Shrier
Keyword(s):  
Connexin 43 ◽  
Cell Types ◽  
Ph Homeostasis ◽  
Adult Rat ◽  
Junction Protein ◽  
Close Proximity ◽  
Gap Junction Protein ◽  
Intercalated Disks ◽  
Distinct Distribution ◽  
Intercalated Disk

The Na+/H+exchanger NHE1 isoform is an integral component of cardiac intracellular pH homeostasis that is critically important for myocardial contractility. To gain further insight into its physiological significance, we determined its cellular distribution in adult rat heart by using immunohistochemistry and confocal microscopy. NHE1 was localized predominantly at the intercalated disk regions in close proximity to the gap junction protein connexin 43 of atrial and ventricular muscle cells. Significant labeling of NHE1 was also observed along the transverse tubular systems, but not the lateral sarcolemmal membranes, of both cell types. In contrast, the Na+-K+-ATPase α1-subunit was readily labeled by a specific mouse monoclonal antibody (McK1) along the entire ventricular sarcolemma and intercalated disks and, to a lesser extent, in the transverse tubules. These results indicate that NHE1 has a distinct distribution in heart and may fulfill specialized roles by selectively regulating the pH microenvironment of pH-sensitive proteins at the intercalated disks (e.g., connexin 43) and near the cytosolic surface of sarcoplasmic reticulum cisternae (e.g., ryanodine receptor), thereby influencing impulse conduction and excitation-contraction coupling.

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