Single‐cell analysis of osmoregulation reveals heterogeneity of aquaporin 4 functionality in human astrocytes DOI Open Access

Hugo Steenberghen,

Sarah De Beuckeleer, Niels Hellings

et al.

Cytometry Part A, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 6, 2024

The water channel aquaporin 4 (AQP4) contributes to flow and waste removal across the blood-brain barrier its levels, organization localization are perturbed in various neurological diseases, including Alzheimer's Disease. This renders AQP4 a potentially valuable therapeutic target. However, most functional assays aimed at identifying modulators of function performed with primary rodent cells do not consider inter-cellular variations abundance presentation. To address this, we have established applied robust live cell microscopy assay that captures contribution osmotically driven (de-)quenching vital dye Calcein-AM single-cell resolution. Using human astrocytoma cells, found performing measurements on cellular regions instead whole fields view yielded more sensitive readout osmotic response, which correlated abundance. Stable co-expression two major isoforms, but individual provoked faster adaptation changes, while siRNA-mediated knockdown had opposite effect. Post-hoc correlation canonical membrane marker CD44 revealed speed response scaled enrichment. Coating substrate laminin promoted enrichment, confinement fixed-size micropatterns further increased osmoregulation, underscoring influence extracellular factors. fetal astrocytes iPSC-derived astrocyte models was comparable AQP4-deficient line their low levels indicative immature state. In conclusion, correlative approach based quantification quenching capacity, allows resolving osmoregulation manner reveals heterogeneity between within (-like) cultures, could prove crucial for future screens modulators.

Language: Английский

Nanoparticle Association with Brain Cells Is Augmented by Protein Coronas Formed in Cerebrospinal Fluid DOI
Claire Rennie, Nabila Morshed, Matthew Faria

et al.

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Neuronanomedicine harnesses nanoparticle technology for the treatment of neurological disorders. An unavoidable consequence delivery to biological systems is formation a protein corona on surface. Despite well-established influence behavior and fate, as well FDA approval neuro-targeted nanotherapeutics, effect physiologically relevant nanoparticle-brain cell interactions insufficiently explored. Indeed, less than 1% studies have investigated coronas formed in cerebrospinal fluid (CSF), surrounding brain. Herein, we utilize two clinically polymeric nanoparticles (PLGA PLGA-PEG) evaluate serum CSF coronas. LC-MS analysis revealed distinct compositions, with selective enrichment/depletion profiles. Enhanced association precoated particles brain cells demonstrates importance selecting fluids more accurately study subsequent nanoparticle-cell interactions, paving way improved engineering vivo applications.

Language: Английский

Citations

1
Peroxiporins and Oxidative Stress: Promising Targets to Tackle Inflammation and Cancer DOI Open Access
Inês V. da Silva, Monika Mlinarić,

Ana Rita Lourenço

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8381 - 8381

Published: Aug. 1, 2024

Peroxiporins are a specialized subset of aquaporins, which integral membrane proteins primarily known for facilitating water transport across cell membranes. In addition to the classical function, peroxiporins have unique capability hydrogen peroxide (H2O2), reactive oxygen species involved in various cellular signaling pathways and regulation oxidative stress responses. The H2O2 levels is crucial maintaining homeostasis, play significant role this process by modulating its intracellular extracellular concentrations. This ability facilitate passage positions as key players redox biology signaling, with implications understanding treating diseases linked inflammation. review provides updated information on physiological roles their disease, emphasizing potential novel biomarkers drug targets conditions where they dysregulated, such inflammation cancer.

Language: Английский

Citations

6
Induction of aquaporins by plasma of patients with systemic lupus erythematosus DOI
Hussein Baharlooi, Samaneh Enayati, Nooshin Ahmadzadeh

et al.

Expert Review of Clinical Immunology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 8

Published: May 5, 2025

Systemic lupus erythematosus is a chronic, multisystemic, inflammatory disease. Aquaporins, group of transmembrane channels, are known to help prime immune cells and their migration. In this study, qRT-PCR analysis was performed identify aquaporins whose expression in SLE patients associated with the profile B cells. A stable healthy line cultured subjected plasma obtained from or individuals for 1 week. Subsequently, gene assessed using real-time PCR. The findings showed that treated had different profiles genes, including TNF-α, IFN-γ, CD40, TNFSF13B, TNFRSF13C. study also revealed abnormal patterns (AQP3, AQP6, AQP8, AQP9) SLE-treated group. Among AQP3, AQP9, AQP11 were differently correlated phenotype These genes may play role pathogenesis by affecting cell proliferation, regulation, inflammation, cytokine processing. suggest can induce lymphocytes key aquaporin which could impact development SLE.

Language: Английский

Citations

0
Functional characterization of CatTohm, a mouse AQP0 mutation that causes oxidative stress, cytotoxicity, dominant congenital lens cataract and microphthalmia DOI
S. Sindhu Kumari, Tadashi Okamura, Kulandaiappan Varadaraj

et al.

Experimental Eye Research, Journal Year: 2025, Volume and Issue: unknown, P. 110434 - 110434

Published: May 1, 2025

Language: Английский

Citations

0
Aquaporin 4 and the endocannabinoid system: a potential therapeutic target in brain injury DOI Creative Commons

Ari Misael Martínez-Torres,

Julio Morán

Experimental Brain Research, Journal Year: 2024, Volume and Issue: 242(9), P. 2041 - 2058

Published: July 23, 2024

Brain edema is a critical complication arising from stroke and traumatic brain injury (TBI) with an important impact on patient recovery can lead to long-term consequences. Therapeutic options reduce progression are limited variable outcomes. Aquaporin 4 (AQP4) water channel that allows bidirectional diffusion across the astrocyte membrane participates in distinct phases of cerebral edema. The absence or inhibition this has been demonstrated ameliorate damage. endocannabinoid system (ECS) neuromodulator wide expression its activation shown neuroprotective properties diverse models neuronal This review describes discusses major features ECS AQP4 their role during damage, observing stimulation reduces size however, relationship between dynamics remains unclear. research these topics holds promising therapeutic implications for treatment following TBI.

Language: Английский

Citations

2
Protein Coronas Derived from Cerebrospinal Fluid Enhance the Interactions Between Nanoparticles and Brain Cells DOI Creative Commons
Nabila Morshed, Claire Rennie, Matthew Faria

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 3, 2024

Abstract Neuronanomedicine harnesses nanoparticle technology for the treatment of neurological disorders. An unavoidable consequence delivery to biological systems is formation a protein corona on surface. Despite well-established influence behavior and fate, as well FDA approval neuro-targeted nanotherapeutics, effect physiologically relevant nanoparticle-brain cell interactions insufficiently explored. Indeed, less than 1% studies have investigated coronas formed in cerebrospinal fluid (CSF), surrounding brain. Herein, we utilize two clinically polymeric nanoparticles (PLGA PLGA-PEG) evaluate serum CSF coronas. LC-MS analysis revealed distinct compositions, with selective enrichment/depletion profiles. Following incubation brain cells, PLGA particles showed enhanced associations all types compared their corresponding PLGA-PEG particles. CSF-derived nanoparticles, specifically, greatest nanoparticle-cell interactions, Pearson’s correlation revealing that proteins associated were exclusively enriched this corona. This study demonstrates importance correct choice fluids, its corona, subsequent interactions.

Language: Английский

Citations

1
Effect of hydrogen peroxide on lens transparency, intracellular pH, gap junction coupling, hydrostatic pressure and membrane water permeability DOI
Kulandaiappan Varadaraj, Junyuan Gao,

Richard T. Mathias

et al.

Experimental Eye Research, Journal Year: 2024, Volume and Issue: 245, P. 109957 - 109957

Published: June 5, 2024

Language: Английский

Citations

1
Serum-derived Protein Coronas Affect Nanoparticle Interactions with Brain Cells DOI Creative Commons
Nabila Morshed, Claire Rennie, Wei Deng

et al.

Nanotechnology, Journal Year: 2024, Volume and Issue: 35(49), P. 495101 - 495101

Published: Sept. 19, 2024

Abstract Neuronanomedicine is an emerging field bridging the gap between neuromedicine and novel nanotherapeutics. Despite promise, clinical translation of neuronanomedicine remains elusive, possibly due to a dearth information regarding effect protein corona on these neuronanomedicines. The corona, layer proteins adsorbed nanoparticles following exposure biological fluids, ultimately determines fate in systems, dictating nanoparticle–cell interactions. To date, few studies have investigated interactions with brain-derived cells, important consideration for development Here, two polymeric nanoparticles, poly(lactic-co-glycolic acid) (PLGA) PLGA-polyethylene glycol (PLGA-PEG), were used obtain serum-derived coronas. Protein characterization liquid chromatography mass spectrometry analysis revealed distinct differences biophysical properties composition. PLGA coronas contained high abundance globins (60%) apolipoproteins (21%), while PLGA-PEG fewer (42%) protease inhibitors (28%). Corona coated readily internalized into microglia neuronal but not astrocytes. Internalization was associated pro-inflammatory cytokine release decreased cell viability, however, viability rescued cells treated nanoparticles. These results showcase importance mediating

Language: Английский

Citations

0
Single‐cell analysis of osmoregulation reveals heterogeneity of aquaporin 4 functionality in human astrocytes DOI Open Access

Hugo Steenberghen,

Sarah De Beuckeleer, Niels Hellings

et al.

Cytometry Part A, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 6, 2024

The water channel aquaporin 4 (AQP4) contributes to flow and waste removal across the blood-brain barrier its levels, organization localization are perturbed in various neurological diseases, including Alzheimer's Disease. This renders AQP4 a potentially valuable therapeutic target. However, most functional assays aimed at identifying modulators of function performed with primary rodent cells do not consider inter-cellular variations abundance presentation. To address this, we have established applied robust live cell microscopy assay that captures contribution osmotically driven (de-)quenching vital dye Calcein-AM single-cell resolution. Using human astrocytoma cells, found performing measurements on cellular regions instead whole fields view yielded more sensitive readout osmotic response, which correlated abundance. Stable co-expression two major isoforms, but individual provoked faster adaptation changes, while siRNA-mediated knockdown had opposite effect. Post-hoc correlation canonical membrane marker CD44 revealed speed response scaled enrichment. Coating substrate laminin promoted enrichment, confinement fixed-size micropatterns further increased osmoregulation, underscoring influence extracellular factors. fetal astrocytes iPSC-derived astrocyte models was comparable AQP4-deficient line their low levels indicative immature state. In conclusion, correlative approach based quantification quenching capacity, allows resolving osmoregulation manner reveals heterogeneity between within (-like) cultures, could prove crucial for future screens modulators.

Language: Английский

Citations

0