Mxene-bpV plays a neuroprotective role in cerebral ischemia-reperfusion injury by activating the Akt and promoting the M2 microglial polarization signaling pathways.

Autor: Cheng J; Department of Neurosurgery, Renmin Hospital of Wuhan University, 99 Zhang Zhidong Street, Wuhan, 430060, China., Yu H; Department of Pathology, Xiangyang No.1 People's Hospital, Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Xiangyang City, Department of Obstetrics and Gynaecology, Hubei Provincial Clinical Research Center for Accurate Fetus Malformation Diagnosis, Hubei University of Medicine, Xiangyang, 441000, China., Zhang ZF; Department of Physiology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, 442000, China., Jiang HX; Department of Neurosurgery, Renmin Hospital of Wuhan University, 99 Zhang Zhidong Street, Wuhan, 430060, China., Wu P; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325000, China., Wang ZG; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325000, China. wzhouguang@gmail.com., Chen ZB; Department of Neurosurgery, Renmin Hospital of Wuhan University, 99 Zhang Zhidong Street, Wuhan, 430060, China. chzbiao@126.com., Wu LQ; Department of Neurosurgery, Renmin Hospital of Wuhan University, 99 Zhang Zhidong Street, Wuhan, 430060, China. Wuliquan@whu.edu.cn.
Jazyk: angličtina
Zdroj: 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.
DOI: 10.1007/s10856-024-06811-0
Abstrakt: 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 3 C 2 T x ) 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 3 C 2 T x ) 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 473 ) 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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