Interacting Network of the Gap Junction (GJ) Protein Connexin43 (Cx43) is Modulated by Ischemia and Reperfusion in the Heart*

Martins‐Marques, Tânia; Anjo, Sandra I.; Pereira, Paulo; Manadas, Bruno; Girão, Henrique

doi:10.1074/mcp.m115.052894

Cited by 56 publications

(56 citation statements)

References 51 publications

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“…However, it remains to be determined whether this is a direct or indirect interaction in most cases. [67][68][69] Such interaction studies have mostly focussed on Cx43 as it is nearly ubiquitously expressed. In the rat heart, mass spectrometry allowed identification of more than 400 proteins interacting with Cx43.…”

Section: Interactions With Other Proteinsmentioning

confidence: 99%

Connexins in the control of vasomotor function

Pogoda

Kameritsch

Mannell³

et al. 2018

Acta Physiologica

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Vascular endothelial cells, as well as smooth muscle cells, show heterogeneity with regard to their receptor expression and reactivity. For the vascular wall to act as a functional unit, the various cells' responses require integration. Such an integration is not only required for a homogeneous response of the vascular wall, but also for the vasomotor behaviour of consecutive segments of the microvascular arteriolar tree. As flow resistances of individual sections are connected in series, sections require synchronization and coordination to allow effective changes of conductivity and blood flow. A prerequisite for the local coordination of individual vascular cells and different sections of an arteriolar tree is intercellular communication. Connexins are involved in a dual manner in this coordination. (i) By forming gap junctions between cells, they allow an intercellular exchange of signalling molecules and electrical currents. In particular, the spread of electrical currents allows for coordination of cell responses over longer distances. (ii) Connexins are able to interact with other proteins to form signalling complexes. In this way, they can modulate and integrate individual cells' responses also in a channel-independent manner. This review outlines mechanisms allowing the vascular connexins to exert their coordinating function and to regulate the vasomotor reactions of blood vessels both locally, and in vascular networks. Wherever possible, we focus on the vasomotor behaviour of small vessels and arterioles which are the main vessels determining vascular resistance, blood pressure and local blood flow.

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Section: Interactions With Other Proteinsmentioning

confidence: 99%

Connexins in the control of vasomotor function

Pogoda

Kameritsch

Mannell³

et al. 2018

Acta Physiologica

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“…An apparent increase of intercalated Cx43 may be considered as a tendency for cardiac recovery. Martins‐Marques et al have demonstrated that ischemic conditions in the heart impact far‐ranging aspects of Cx43 biology such as its interactome . We also probed Cx43 localization in the aforementioned set of four, patient‐matched, cases of non‐ischemic (dilated) cardiomyopathy (Figure B).…”

Section: Resultsmentioning

confidence: 99%

Impact of left ventricular assist device therapy on the cardiac proteome and metabolome composition in ischemic cardiomyopathy

et al. 2019

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The changes in the myocardial proteome and metabolome associated with left ventricular assist device (LVAD) therapy in patients with ischemic cardiomyopathy (ICM) are poorly characterized. We investigated the impact of mechanical unloading following LVAD therapy on the myocardial proteome and metabolome. Matched samples of 5 patients’ myocardial tissue, harvested at the time of LVAD implant (“pre‐LVAD”) or heart transplant (“post‐LVAD”), were studied by quantitative proteomics and metabolomics as well as being probed for T‐tubule structure and connexin‐43 distribution. Moreover, pre‐LVAD proteome profiles of ICM context were bioinformatically compared to pre‐LVAD proteome profiles of dilated cardiac myopathy (DCM). More than 2120 proteins were reliably identified and quantified in paired patient samples. LVAD therapy led to proteomic remodeling, including reduced levels of α‐1‐antichymotrypsin together with an overall decrease of immune response proteins and an increase of proteins involved in membrane biology. Metabolomics highlighted increased glucose and glucose‐6‐phosphate levels in the left ventricle upon LVAD therapy. Wheat germ agglutinin staining demonstrated improved T‐tubule structure. Connexin‐43 displayed a trend for more pronounced intercalated disc localization. In comparing pre‐LVAD proteome profiles of ICM context with pre‐LVAD proteome profiles of dilated cardiac myopathy (DCM), we noticed an overrepresentation in ICM of proteins associated with humoral immune response. Our findings underline an impact of LVAD therapy on left ventricular biology in ICM. The proteomic, metabolomic, and structural alterations described here are typically associated with cardiac recovery. On the molecular level, our findings indicate the possibility of cardiac remodeling under LVAD therapy in ICM.

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“…The reason was probably due to the interaction of Gja1 with these proteins involved in gene transcription. Indeed, accumulating data have identified a lot of Gja1-interacting partners (Butkevich et al 2004, Singh et al 2005, Dai et al 2007, Martins-Marques et al 2015. However, the regulatory mechanisms of Gja1 on the expression of Ccnd3, Cdk4 and Hand2 in uterine stromal cells remain to be determined.…”

Section: :2mentioning

confidence: 99%

Gja1 acts downstream of Acvr1 to regulate uterine decidualization via Hand2 in mice

Yue

Wang

et al. 2017

Journal of Endocrinology

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Although has been proved to play an important role in uterine decidualization, its regulatory mechanism remains largely unknown. Here, we showed that was highly expressed in the decidual cells and promoted the proliferation of uterine stromal cells and expression of and, which were two well-known differentiation markers for decidualization. Further analysis revealed that might act downstream of and cAMP to regulate the differentiation of uterine stromal cells. Administration of cAMP analog 8-Br-cAMP to siRNA-transfected stromal cells resulted in an obvious increase of expression, whereas PKA inhibitor H89 impeded the induction of elicited by overexpression, indicating that cAMP-PKA signal mediates the regulation of on expression. In uterine stromal cells, knockdown of blocked the cAMP induction of Moreover, siRNA-mediated downregulation of impaired the stimulatory effects of overexpression on the expression of and, whereas constitutive expression of reversed the inhibitory effects of siRNA on stromal differentiation. Meanwhile, might play a vital role in the crosstalk between and Collectively, may act downstream of cAMP-PKA signal to mediate the effects of on the differentiation of uterine stromal cells through targeting.

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Interacting Network of the Gap Junction (GJ) Protein Connexin43 (Cx43) is Modulated by Ischemia and Reperfusion in the Heart*

Cited by 56 publications

References 51 publications

Connexins in the control of vasomotor function

Connexins in the control of vasomotor function

Impact of left ventricular assist device therapy on the cardiac proteome and metabolome composition in ischemic cardiomyopathy

Gja1 acts downstream of Acvr1 to regulate uterine decidualization via Hand2 in mice

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