Connexin 43 Phosphorylation: Implications in Multiple Diseases

Zhang, Meng; Wang, Zhenzhen; Chen, Nai-Hong

doi:10.3390/molecules28134914

Cited by 8 publications

(3 citation statements)

References 139 publications

(160 reference statements)

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“…This limitation can be minimized in the case of the directed transfer of cellular components from cell to cell as a result of the formation of intercellular contacts. Examples of such contacts include the gap junction formed by the connexin 43 protein, which provides intercellular communication, electrical coupling of neighboring cells, and transmission of depolarisation signals [20]. Among the intercellular interactions, the migration of cytoplasmic components between contacting cells along cell processes, particularly tunneling nanotubes, deserves special attention [18,21].…”

Section: Discussionmentioning

confidence: 99%

Cellular cardiomyoplasty for refractory angina: experimental rationale.

Gramatiuk,

Ivanova,

Sargsyan

et al. 2024

Preprint

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This experimental study aimed to investigate the therapeutic potential of cellular cardiomyoplasty in the context of refractory angina using a rodent model. The study comprised five groups of animals subjected to different interventions, including "empty" injections, autologous mesenchymal stem cell (MSC) injections via various routes, and untreated controls. Stress load modeling was employed to assess the hemodynamic response, mainly focusing on heart rate changes during isopropyl norepinephrine loading. Results revealed a positive chronotropic effect in all groups, with varying severity. Intact rats exhibited a significant increase in heart rate, while animals in the "empty" injection group demonstrated a less pronounced response. Interestingly, those treated with MSCs, either through direct myocardial injection or intravenous and intracavitary routes, exhibited notable variations in stress-induced heart rate changes. By the third minute of the experiment, a decrease in heart rate was observed across all groups, stabilizing at 490–495 beats/min. Notably, the groups with untreated myocardial infarction and "empty" injections displayed an inability to compensate for required blood flow during stress, indicative of potential challenges in these conditions. These findings suggest that cellular cardiomyoplasty, particularly with autologous MSCs injected into the myocardium, may influence the stress-induced changes in heart rate. However, a comprehensive evaluation of additional cardiovascular parameters and further exploration of therapeutic outcomes are warranted to elucidate the potential clinical relevance of these observations. This study contributes valuable insights into the experimental rationale and hemodynamic effects of cellular cardiomyoplasty, laying the groundwork for future investigations in refractory angina and myocardial infarction.

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Section: Discussionmentioning

confidence: 99%

Cellular cardiomyoplasty for refractory angina: experimental rationale.

Gramatiuk,

Ivanova,

Sargsyan

et al. 2024

Preprint

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“…Reversible phosphorylation is a dynamic process [ 58 ] that occurs extensively in eukaryotic cells. Its occurrence is typically rare, and abnormal phosphorylation has been linked to certain diseases [ 59 ]. For instance, serum endogenous peptide levels have been proposed as biomarkers for cancer.…”

Section: Progress In Magnetic Mesoporous Materials For Phosphopeptide...mentioning

confidence: 99%

Progress in Core–Shell Magnetic Mesoporous Materials for Enriching Post-Translationally Modified Peptides

Zhu,

Fu,

Zhao

et al. 2024

JFB

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Endogenous peptides, particularly those with post-translational modifications, are increasingly being studied as biomarkers for diagnosing various diseases. However, they are weakly ionizable, have a low abundance in biological samples, and may be interfered with by high levels of proteins, peptides, and other macromolecular impurities, resulting in a high limit of detection and insufficient amounts of post-translationally modified peptides in real biological samples to be examined. Therefore, separation and enrichment are necessary before analyzing these biomarkers using mass spectrometry. Mesoporous materials have regular adjustable pores that can eliminate large proteins and impurities, and their large specific surface area can bind more target peptides, but this may result in the partial loss or destruction of target peptides during centrifugal separation. On the other hand, magnetic mesoporous materials can be used to separate the target using an external magnetic field, which improves the separation efficiency and yield. Core–shell magnetic mesoporous materials are widely utilized for peptide separation and enrichment due to their biocompatibility, efficient enrichment capability, and excellent recoverability. This paper provides a review of the latest progress in core–shell magnetic mesoporous materials for enriching glycopeptides and phosphopeptides and compares their enrichment performance with different types of functionalization methods.

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“…The human genome encodes for 21 connexin genes. Connexin 43 (Cx43) is one of the most well-studied connexin proteins and has been studied in a variety of human tissues and diseases [1][2][3][4][5][6][7][8][9]. We and others have studied the role of Cx43 in breast cancer [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Mapping the Anti-Cancer Activity of α-Connexin Carboxyl-Terminal (aCT1) Peptide in Resistant HER2+ Breast Cancer

Baker,

Abt,

Doud

et al. 2024

Cancers

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Connexin 43 (Cx43) is a protein encoded by the GJA1 gene and is a component of cell membrane structures called gap junctions, which facilitate intercellular communication. Prior evidence indicates that elevated GJA1 expression in the HER2-positive (HER2+) subtype of breast cancer is associated with poor prognosis. Prior evidence also suggests that HER2+ breast cancers that have become refractory to HER2-targeted agents have a loss of Cx43 gap junction intercellular communication (GJIC). In this study, a Cx43-targeted agent called alpha-connexin carboxyl-terminal peptide (aCT1) is examined to determine whether GJIC can be rescued in refractory HER2+ breast cancer cells. A proposed mechanism of action for aCT1 is binding to the tight junction protein Zonal Occludens-1 (ZO-1). However, the true scope of activity for aCT1 has not been explored. In this study, mass spectrometry proteomic analysis is used to determine the breadth of aCT1-interacting proteins. The NanoString nCounter Breast Cancer 360 panel is also used to examine the effect of aCT1 on cancer signaling in HER2+ breast cancer cells. Findings from this study show a dynamic range of binding partners for aCT1, many of which regulate gene expression and RNA biology. nCounter analysis shows that a number of pathways are significantly impacted by aCT1, including upregulation of apoptotic factors, leading to the prediction and demonstration that aCT1 can boost the cell death effects of cisplatin and lapatinib in HER2+ breast cancer cells that have become resistant to HER2-targeted agents.

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Connexin 43 Phosphorylation: Implications in Multiple Diseases

Cited by 8 publications

References 139 publications

Cellular cardiomyoplasty for refractory angina: experimental rationale.

Cellular cardiomyoplasty for refractory angina: experimental rationale.

Progress in Core–Shell Magnetic Mesoporous Materials for Enriching Post-Translationally Modified Peptides

Mapping the Anti-Cancer Activity of α-Connexin Carboxyl-Terminal (aCT1) Peptide in Resistant HER2+ Breast Cancer

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