The Functional Interaction of KATP and BK Channels with Aquaporin-4 in the U87 Glioblastoma Cell
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Lines
2.2. Constructs and Transfection
2.3. Drugs and Solutions
2.4. Antibodies
2.5. Nuclear Staining
2.6. Immunofluorescence and Quantitative Analysis
2.7. Morphological Analysis
2.8. Cell Viability Assay
2.9. Patch-Clamp Experiments
2.10. Polymerase Chain Reaction
2.11. Statistical Analysis
3. Results
3.1. AQP4-OAP Expression in U87 Cells
3.2. Whole-Cell Inward and Outward Macroscopic K+ Currents Recorded in U87wt Cells and Effects of the K+ Channel Modulators on Cell Proliferation
3.3. AQP4 Aggregation State Affects the TEA-K+ Sensitive Currents in U87 Glioma Cells
3.4. AQP4 Aggregation State Changes the Expression Profile of KCNMA1, KCNJ11, ABCC8, and ABCC9 Genes in U87 Glioma Cells
3.5. AQP4 and Kir6.2 Are Involved in Glioma Apoptotic Fate
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Differential Expression/Mutation | Cancers | Information on Analyzed Samples | Consequences | PubMed Code | |
---|---|---|---|---|---|
Upregulation | Glioma | Tissue from 22 patients with newly diagnosed GBM. | [26,27] | ||
Upregulation | Glioma | A total of 50 glioma samples, ranging in grades from II to IV, were collected from a cohort of 35 male and 15 female patients. | Cells exhibiting enhanced migration potential displayed notably high levels of AQP4 expression, indicating a potential association between AQP4 and glioma cell migration. | [28] | |
Upregulation | Brain tumors | The study involved analyzing 5 tumor samples from subependymomas located in the fourth ventricle, as well as subependymoma (SE) tumor samples found supratentorial with relation to the first to the third ventricle. | Increased AQP4 expression has been observed in malignant tumors, where it appears to contribute to edema formation, invasive growth, and tumor recurrence. However, AQP4 does not play a significant role in benign tumors. | [29] | |
AQP4 | Upregulation | GBM | The tumor samples from 14 patients with primary glioblastomas. | [30] | |
Upregulation | Brain tumors/GBM | Tissue samples from brain tumors of 26 patients. | Analysis of GBM samples showed that increased AQP4 expression, loss of cellular polarity, and matrix alterations are linked to more severe glioblastoma and cerebral edema. This highlights AQP4’s role in tumor malignancy, suggesting it as a potential therapeutic target. | [31] | |
Upregulation (AQP4-tetramer and AQP4-OAP) | Brain tumors/GBM | Tumor tissues obtained from a total of 22 patients diagnosed with astrocytoma of WHO grades II, III, and IV, and an additional patient diagnosed with glioblastoma multiforme (GBM), were included in the study. | Upregulation of AQP4-tetramers and mRNA-AQP4-OAPs in all astrocytomas, but the AQP4-OAP’s/AQP4-tetramer’s ratio differed from 1.14 to 1.5 in low-grade astrocytomas and to 1.94 in glioblastomas. This could have a possible impact on the development of new therapies. | [28] | |
Upregulation | Brain tumors/GBM | Brain tumors and the corresponding adjacent tissues from 30 patients diagnosed with glioblastoma. | The overexpression of AQP4 was observed in both brain tumors and the adjacent tissues, and this heightened expression was found to be correlated with the extent of brain edema. | [32] | |
Downregulation | Brain tumors/GBM | A total of 16 tissue samples were collected from various regions within the tumoral core. | The presence of AQP4 alterations in GBMs appears to play a role in edema formation. Therefore, AQP4 could be viewed as a promising early biomarker for tracking GBM progression and also as a potential target for AQP4 modulation in therapeutic approaches. | [33] | |
KATP | |||||
Upregulation of ABCC8 | Glioma | The information is based on the analysis of 1893 human glioma samples from four independent databases. | Glioma chemosensitivity can be predicted by high ABCC8 mRNA expression, whereas low ABCC8 mRNA expression can serve as an indicator of glioma sensitivity to radiotherapy. | [34] | |
Upregulation of ABCC8 | Brain tumors | The information comes from the analysis of human tissue samples from 6 glioblastoma, 12 brain metastases, 11 medulloblastoma, 9 supratentorial ependymomas, and 8 posterior fossa ependymomas. | SUR1 is a potential therapeutic target for reducing neuroinflammation in adult and pediatric brain tumors. Inhibition of SUR1 induces neuronal stabilization in glioblastoma, brain metastases, and posterior fossa ependymoma, as well as edema reduction in medulloblastoma. | [35] | |
Upregulation of KCNJ8 and ABCC8 | Glioma | 20 human glioma biopsies. | The Kir6.2 and SUR1 subunits of the KATP channel are involved in the proliferation of U87 and U251 glioma cells. The KATP channel inhibitors significantly reduced the growth curve. On the other hand, KATP channel agonists promoted the proliferation of U87 and U251 cells. | [36] | |
BK | Upregulation of KCNMA1 | Glioma | Biopsies from patients with malignant gliomas. | The expression of BK channels has shown a positive correlation with tumor malignancy grades, indicating a significant role for the gBK channel in glioma biology. Utilizing BK channel agonists could potentially be advantageous for brain tumor patients, as they might enhance the delivery of anti-neoplastic agents to brain tumors. | [37] |
Upregulation of KCNMA1 | Brain tumors | Sample tissues from patients with malignant gliomas. | [38] |
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Maqoud, F.; Simone, L.; Tricarico, D.; Camerino, G.M.; Antonacci, M.; Nicchia, G.P. The Functional Interaction of KATP and BK Channels with Aquaporin-4 in the U87 Glioblastoma Cell. Biomedicines 2024, 12, 1891. https://doi.org/10.3390/biomedicines12081891
Maqoud F, Simone L, Tricarico D, Camerino GM, Antonacci M, Nicchia GP. The Functional Interaction of KATP and BK Channels with Aquaporin-4 in the U87 Glioblastoma Cell. Biomedicines. 2024; 12(8):1891. https://doi.org/10.3390/biomedicines12081891
Chicago/Turabian StyleMaqoud, Fatima, Laura Simone, Domenico Tricarico, Giulia Maria Camerino, Marina Antonacci, and Grazia Paola Nicchia. 2024. "The Functional Interaction of KATP and BK Channels with Aquaporin-4 in the U87 Glioblastoma Cell" Biomedicines 12, no. 8: 1891. https://doi.org/10.3390/biomedicines12081891