The neuroprotective role of propofol in transient global and focal cerebral ischemia reperfusion (I/R) animal model has recently been highlighted. However, no studies have conducted to explore the relationship between mitochondrial fission/fusion and I/R injury under the intervention of propofol. Moreover, neuroprotective mechanism of propofol is yet unclear. Culturing primary hippocampal cells were subjected to oxygen-glucose deprivation and re-oxygenation (OGD/R) model, as a model of cerebral I/R in vitro. Methods CCK-8 assay was used to test the effect of propofol on cell viability. We examined the effect of propofol on mitochondrial ultrastructure and mitochondrial fission evoked by OGD/R with transmission electron microscopy and immunofluorescence assay. To investigate possible neuroprotective mechanisms, the authors then examined whether propofol could inhibit calcium-overload, calcineurin (CaN) activation and the phosphorylation of dynamin-related protein 1 (Drp1) during the period of OGD/R, as well as the combination of Drp1-ser 637 and fission 1 (Fis1) protein by immunofluorescence assay, ELISA and double-labeling immunofluorescence analysis. Finally, the expression of Drp1-ser 637 and Fis1, apoptosis inducing factor (AIF) and cytochrome C (Cyt C) were detected by western blot. When added in culture media during OGD period, propofol (0.1μM-50μM) could alleviate neurons injury and protect mitochondrial ultrastructure, meanwhile inhibit mitochondrial fission. Furthermore, the concentration of intracellular free Ca2+, CaN activition and the phosphorylation of Drp1-ser637 were suppressed, as well as the translocation and combination of Drp1-ser 637 and Fis1. The authors also found that the expression of Cyt C, AIF, Drp1-ser637 and Fis1 were down-regulated. Notably, high dose of propofol (100μM-200μM) were confirmed to decrease the survival of neurons based on results of cell viability. Propofol could inhibit mitochondrial fission and mitochondrial apoptotic pathway evoked by OGD/R in rat hippocampal neurons, which may be via depressing calcium-overload.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5082830 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0165052 | PLOS |
Publication Analysis
Top Keywords
Similar Publications
The Role of Breast Milk Cell-Free DNA in the Regulation of the Neonatal Immune Response.
Nutrients
December 2024
Liggins Institute, University of Auckland, Auckland 1023, New Zealand.
The neonatal period is a critical phase for the development of the intestinal immune system, marked by rapid adaptation to the external environment and unique nutritional demands. Breast milk plays a pivotal role in this transition, yet the mechanisms by which it influences neonatal mucosal immunity remain unclear. This review examines the potential mechanisms by which cell-free DNA (cfDNA) in breast milk may impact neonatal immune development, particularly through Toll-like receptor 9 (TLR9) signalling and gut microbiota interactions.
View Article and Find Full Text PDFSexual Dimorphism of Ethanol-Induced Mitochondrial Dynamics in Purkinje Cells.
Int J Mol Sci
December 2024
Department of Anesthesiology and the Center for Shock, Trauma and Anesthesiology Research (S.T.A.R.), University of Maryland School of Medicine, 685 Baltimore St., Baltimore, MD 21201, USA.
The cerebellum, a key target of ethanol's toxic effects, is associated with ataxia following alcohol consumption. However, the impact of ethanol on Purkinje cell (PC) mitochondria remains unclear. To investigate how ethanol administration affects mitochondrial dynamics in cerebellar Purkinje cells, we employed a transgenic mouse model expressing mitochondria-targeted yellow fluorescent protein in Purkinje cells (PC-mito-eYFP).
View Article and Find Full Text PDFFunctional Roles of the Charged Residues of the C- and M-Gates in the Yeast Mitochondrial NAD Transporter Ndt1p.
Int J Mol Sci
December 2024
Department of Biosciences, Biotechnology and Environment, University of Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, Italy.
Mitochondrial carriers transport organic acids, amino acids, nucleotides and cofactors across the mitochondrial inner membrane. These transporters consist of a three-fold symmetric bundle of six transmembrane α-helices that encircle a pore with a central substrate binding site, whose alternating access is controlled by a cytoplasmic and a matrix gate (C- and M-gates). The C- and M-gates close by forming two different salt-bridge networks involving the conserved motifs [YF][DE]XX[KR] on the even-numbered and PX[DE]XX[KR] on the odd-numbered transmembrane α-helices, respectively.
View Article and Find Full Text PDFHost-Parasite Interactions in -Infected Cells: Roles of Mitochondria, Microtubules, and the Parasitophorous Vacuole.
Int J Mol Sci
December 2024
Department of Biochemistry and Molecular Biology, Frederick P. Whiddon College of Medicine, Mobile, AL 36688, USA.
An intracellular protozoan, the Apicomplexan parasite () infects nucleated cells, in which it triggers the formation of a specialized membrane-confined cytoplasmic vacuole, named the parasitophorous vacuole (PV). One of the most prominent events in the parasite's intracellular life is the congregation of the host cell mitochondria around the PV. However, the significance of this event has remained largely unsolved since the parasite itself possesses a functional mitochondrion, which is essential for its replication.
View Article and Find Full Text PDFIdentification of Potential Sepsis Therapeutic Drugs Using a Zebrafish Rapid Screening Approach.
Life (Basel)
December 2024
Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
In the military, combat wound infections can progress rapidly to life-threatening sepsis. The discovery of effective small-molecule drugs to prevent and/or treat sepsis is a priority. To identify potential sepsis drug candidates, we used an optimized larval zebrafish model of endotoxicity/sepsis to screen commercial libraries of drugs approved by the U.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!