Bone marrow mesenchymal stem cells conditioned medium protects VSC4.1 cells against 2,5-hexanedione-induced autophagy via NGF-PI3K/Akt/mTOR signaling pathway. 2018

Xin Zhang, and Ying Kong, and Yijie Sun, and Zhiqiang Qian, and Chenxue Gao, and Xiaoxia Shi, and Shuangyue Li, and Yongjun Piao, and Fengyuan Piao
Department of Occupational and Environmental Health, Dalian Medical University, Dalian 116044, China; Department of Clinical Nutrition, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.

We aimed to investigate the effects of bone marrow mesenchymal stem cell conditioned medium (BMSC-CM) in preventing 2,5-hexanedione (HD)-induced damage to motoneurons, and examined the molecular mechanisms that mediate these effects. VSC4.1 cells were exposed to 25 mM HD for 24 h followed by incubation with DMEM for 24 h. HD-treated cells were incubated with BMSC-CM at varied concentrations. Incubation with BMSC-CM ameliorated the decreased cell viability and reduced LDH release from cells exposed to HD. BMSC-CM suppressed the elevated number of autophagic vacuoles, cells with LC3 puncta, increased LC3-II/LC3-I ratio, and decreased p62 caused by HD exposure. BMSC-CM elevated NGF and p-TrkA expressions in HD-treated cells. Administration of NGF inhibited autophagy, an effect that was similar to that observed after BMSC-CM treatment; this effect was abolished by the addition of NGF-neutralizing antibodies. BMSC-CM or NGF elevated p-protein kinase B (Akt) and p-mammalian target of rapamycin (mTOR) in HD-exposed cells, which was interrupted by TrkA inhibitor, K252a and mTOR inhibitor, rapamycin. BMSC-CM prevented HD-induced autophagic cell damage in VSC4.1 cells. The neuroprotective effect of BMSC-CM appeared to be at least partly associated with its ability to trigger the NGF-phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR signaling pathway.

UI MeSH Term Description Entries
D008297 Male Males
D001854 Bone Marrow Cells Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells. Bone Marrow Cell,Cell, Bone Marrow,Cells, Bone Marrow,Marrow Cell, Bone,Marrow Cells, Bone
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D006588 Hexanones 6-carbon straight-chain or branched ketones. Butyl Methyl Ketones,Ethyl Propyl Ketones,Ketones, Butyl Methyl,Ketones, Ethyl Propyl,Methyl Ketones, Butyl,Propyl Ketones, Ethyl
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001343 Autophagy The segregation and degradation of various cytoplasmic constituents via engulfment by MULTIVESICULAR BODIES; VACUOLES; or AUTOPHAGOSOMES and their digestion by LYSOSOMES. It plays an important role in BIOLOGICAL METAMORPHOSIS and in the removal of bone by OSTEOCLASTS. Defective autophagy is associated with various diseases, including NEURODEGENERATIVE DISEASES and cancer. Autophagocytosis,ER-Phagy,Lipophagy,Nucleophagy,Reticulophagy,Ribophagy,Autophagy, Cellular,Cellular Autophagy,ER Phagy
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D017077 Culture Media, Conditioned Culture media containing biologically active components obtained from previously cultured cells or tissues that have released into the media substances affecting certain cell functions (e.g., growth, lysis). Conditioned Culture Media,Conditioned Culture Medium,Conditioned Media,Conditioned Medium,Culture Medium, Conditioned,Media, Conditioned,Medium, Conditioned
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis

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