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This study demonstrated that both copper oxide nanoparticles (CuO‐NPs) and copper nanoparticles (Cu‐NPs) can cause swelling, inflammation, and cause damage to the mitochondria of alveolar type II epithelial cells in mice. Cellular examinations indicated that both CuO‐NPs and Cu‐NPs can reduce cell viability and harm the mitochondria of human bronchial epithelial cells, particularly Beas‐2B cells. However, it is clear that CuO‐NPs exhibit a more pronounced detrimental effect compared with Cu‐NPs. Using bafilomycin A1 (Bafi A1), an inhibitor of lysosomal acidification, was found to enhance cell viability and alleviate mitochondrial damage caused by CuO‐NPs. Additionally, Bafi A1 also reduces the accumulation of dihydrolipoamide S‐acetyltransferase (DLAT), a marker for mitochondrial protein toxicity, induced by CuO‐NPs. This observation suggests that the toxicity of CuO‐NPs depends on the distribution of copper particles within cells, a process facilitated by the acidic environment of lysosomes. The release of copper ions is thought to be triggered by the acidic conditions within lysosomes, which aligns with the lysosomal Trojan horse mechanism. However, this association does not seem to be evident with Cu‐NPs. In mice, CuO‐NPs caused more extensive lung tissue damage than Cu‐NPs. In Beas‐2B cells, inhibition of lysosomal acidification with Bafi A1 markedly decreased CuO‐NPs‐induced mitochondrial damage. The lysosomal Trojan horse mechanism of aggravates CuO‐NPs‐induced cuproptosis in Beas‐2B cells, which can be reversed by Bafi A1. [ABSTRACT FROM AUTHOR]

Background: This study aimed to overexpress or silence connexin 43 (Cx43) and A‐kinase anchoring protein 95 (AKAP95) in human A549 cells to explore their effects on cyclins and on G1/S conversion when the interrelationship of Cx43, AKAP95, and cyclin E1/E2 changes. Methods: The study mainly used Western blot analysis and Co‐immuno precipitation to detect the target protein in Cx43/AKAP95 over expressed human A549 cells, and the relationship of proteins Cx43, AKAP95 and Cyclin E during G1‐S phase was explored with qualitative and quantitative analysis. Results: The overexpression of Cx43 inhibited the expression of cyclin D1 and E1 by accelerating their degradation and reduced the Cdk2 activity that blocked the DNA transcription activity. However, the overexpression of AKAP95 increased the expression of cyclin D1 and E1 and inhibited their degradation, and enhanced the Cdk2 activity that promoted the DNA transcription activity. Cx43 and AKAP95 competitively bound to cyclin E1/E2, and the competitive binding affected the Cdk2 activity, Rb phosphorylation, DNA transcription activity, and G1/S conversion. Conclusions: This study showed that the expression of ERK1/2, PKA, and PKB increased when BEAS‐2B cells were treated with PDGF‐BB, suggesting that ERK1/2, PKA, and PKB might be involved in the binding of AKAP95 with cyclin E, or the separation of AKAP95 from Cx43 from cyclin E1/E2. The specific mechanism underlying this process still needs further exploration. [ABSTRACT FROM AUTHOR]

Background This study was conducted to investigate the exchange protein directly activated by c AMP ( Epac1), PDE4, and PKC expression in breast cancer tissues, and the correlation between these proteins and AKAP95, Cx43, cyclin D2, and cyclin E1. Methods PV-9000 two-step immunohistochemistry was used to analyze protein expression. Results The positive rate of Epac1 protein expression in breast cancer tissues (58%) was higher than in para-carcinoma tissues (10%) ( P < 0.05). There were no significant differences in the positive rates of PDE4 and PKC expression between breast cancer and para-carcinoma tissues ( P > 0.05). The positive expression rate of PDE4 was higher in the P53 protein positive group compared to the P53 negative group ( P < 0.05). Correlations between Epac1 and cyclin D2, PDE4 and cyclin D2, AKAP95 and PKC, Cx43 and PKC, and cyclin D2 and PKC proteins were observed ( P < 0.05). Conclusion Epac1 expression in breast cancer tissues was increased, suggesting that the protein may be involved in the development of breast cancer. Correlations between Epac1 and cyclin D2, PDE4 and cyclin D2, AKAP95 and PKC, Cx43 and PKC, and cyclin D2 and PKC proteins suggested synergistic effects among these proteins in the development of breast cancer. [ABSTRACT FROM AUTHOR]

A-kinase anchoring protein 95 (AKAP95) functions as a scaffold for protein kinase A. Prior work by our group has shown that AKAP95, in coordination with Connexin 43 (Cx43), modulates the expression of cyclin D and E proteins, thus affecting the cell cycle progression in lung cancer cells. In the current study, we confirmed that AKAP95 forms a complex with Cx43. Moreover, it associates with cyclins D1 and E1 during the G1 phase, leading to the formation of protein complexes that subsequently translocate to the nucleus. These findings indicate that AKAP95 might facilitate the nuclear transport of cyclins D1 and E1. Throughout this process, AKAP95 and Cx43 collectively regulate the expression of cyclin D, phosphorylate cyclin E1 proteins, and target their specific ubiquitin ligases, ultimately impacting cell cycle progression., (© 2024 Wiley Periodicals LLC.)

Vessel development in the yolk sac is important for the embryo development and the malfunction of which can lead to cardiac dysfunction, embryonic malformation and miscarriage. Although substantial emphasis has been placed on the yolk sac vascular remodeling, no detailed three-dimensional (3D) imaging and quantitative analysis of this process has been described. Herein, we explored the development of the vascular system in the visceral yolk sac (VYS) on E11.5, E12.5 and E13.5 mouse embryos using a home-built large field-of-view (FOV) optical-resolution photoacoustic microscopy (OR-PAM). The results showed that OR-PAM can be used as a label-free imaging tool for studying the 2D/3D morphology changes of the vascular system during organogenesis. In addition, after a quantitative analysis the results showed that the microvascular density in the VYS gradually reduced along with the embryo growth. Vascular density in the VYS of E11.5 mouse embryos was almost 6-fold than that of E13.5. Hovever, the averaged vessel diameter of the entire VYS membrane increased gradually with the development of embryos. This study suggests that OR-PAM is a potential tool for acquiring the hemodynamic parameters of mammalian embryos, which could be further used for studying diseases related with the vascular remodeling such as vascular malformations and heart defects., Competing Interests: The authors declare that there are no conflicts of interest., (© 2019 Xiamen University.)

Introduction: The exchange protein directly activated by cAMP (Epac1), a downstream target of the second messenger cAMP, modulates multiple biological effects of cAMP, alone or in cooperation with protein kinase A (PKC). Epac1 is necessary for promoting protein kinase C (PKC) translocation and activation. The aim of the study was to assess the intensity of Epac1 and protein kinase C (PKC) immunoreactivity in lung cancer and para-carcinoma tissues, and their associations with clinical-pathological indexes. Correlations between the immunoreactivity of Epac1, PKC, A-kinase anchor protein 95 (AKAP95) and connexin43 (Cx43) were also examined., Material and Methods: Epac1, Cx43 (46 cases) and PKC, AKAP95 (45 cases) immunoexpression levels were determined in tissue samples of lung cancer and in 12 samples of neighboring para-carcinoma specimens by the PV-9000 Two-step immunohistochemical technique., Results: The percentage of Epac1 positive samples was significantly lower in lung cancer tissue than in neighboring para-carcinoma specimens (37% vs. 83.3%, p < 0.05); the difference in PKC immunoreactivity was not significant (64.4% vs. 91.7%). Epac1 expression was associated with the degree of malignancy and lymph node metastasis (P < 0.05), but not with histological type (P > 0.05), whereas PKC expression was not related to these parameters. Interestingly, Epac1 expression was correlated with PKC and Cx43 expression. Moreover, PKC expression was correlated with AKAP95 expression., Conclusion: Normal Epac1 expression may suppress lung cancer occurrence and metastasis, and its downregulation is involved in cell cycle progression in lung cancer through PKC and Cx43 regulation.