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Mxene-bpV plays a neuroprotective role in cerebral ischemia-reperfusion injury by activating the Akt and promoting the M2 microglial polarization signaling pathways.
- Source :
-
Journal of materials science. Materials in medicine [J Mater Sci Mater Med] 2024 Jul 29; Vol. 35 (1), pp. 42. Date of Electronic Publication: 2024 Jul 29. - Publication Year :
- 2024
-
Abstract
- Studies have shown that the inhibition of phosphatase and tensin homolog deleted on chromosome 10 (PTEN)was neuroprotective against ischemia/reperfusion(I/R) injury. Bisperoxovanadium (bpV), a derivative of vanadate, is a well-established inhibitor of PTEN. However, its function islimited due to its general inadequacy in penetrating cell membranes. Mxene(Ti <subscript>3</subscript> C <subscript>2</subscript> T <subscript>x</subscript> ) is a novel two-dimensional lamellar nanomaterial with an excellent ability to penetrate the cell membrane. Yet, the effects of this nanomaterial on nervous system diseases have yet to be scrutinized. Here, Mxene(Ti <subscript>3</subscript> C <subscript>2</subscript> T <subscript>x</subscript> ) was used for the first time to carry bpV(HOpic), creating a new nanocomposite Mxene-bpV that was probed in a cerebral I/R injury model. The findings showed that this synthetic Mxene-bpV was adequately stable and can cross the cell membraneeasily. We observed that Mxene-bpV treatment significantly increased the survival rate of oxygen glucose deprivation/reperfusion(OGD/R)--insulted neurons, reduced infarct sizes and promoted the recovery of brain function after mice cerebral I/R injury. Crucially, Mxene-bpV treatment was more therapeutically efficient than bpV(HOpic) treatment alone over the same period. Mechanistically, Mxene-bpV inhibited the enzyme activity of PTEN in vitro and in vivo. It also promoted the expression of phospho-Akt (Ser <superscript>473</superscript> ) by repressing PTEN and then activated the Akt pathway to boost cell survival. Additionally, in PTEN transgenic mice, Mxene-bpV suppressed I/R-induced inflammatory response by promoting M2 microglial polarization through PTEN inhibition. Collectively, the nanosynthetic Mxene-bpV inhibited PTEN' enzymatic activity by activating Akt pathway and promoting M2 microglial polarization, and finally exerted neuroprotection against cerebral I/R injury.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Mice
Male
Mice, Inbred C57BL
Brain Ischemia drug therapy
Brain Ischemia pathology
Cell Polarity drug effects
Neurons drug effects
Neurons metabolism
Nanocomposites chemistry
Microglia drug effects
Microglia metabolism
Proto-Oncogene Proteins c-akt metabolism
Reperfusion Injury drug therapy
Reperfusion Injury prevention & control
Signal Transduction drug effects
Neuroprotective Agents pharmacology
Vanadium Compounds pharmacology
Vanadium Compounds chemistry
PTEN Phosphohydrolase metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1573-4838
- Volume :
- 35
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of materials science. Materials in medicine
- Publication Type :
- Academic Journal
- Accession number :
- 39073469
- Full Text :
- https://doi.org/10.1007/s10856-024-06811-0