The Experts below are selected from a list of 1297869 Experts worldwide ranked by ideXlab platform
Rongbiao Pi - One of the best experts on this subject based on the ideXlab platform.
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mef2d mediates the neuroprotective effect of methylene blue against glutamate induced oxidative damage in ht22 hippocampal cells
Molecular Neurobiology, 2017Co-Authors: Ziwei Chen, Wenming Li, Jingkao Chen, Xiaojuan Chao, Qian Yang, Rongbiao PiAbstract:Methylene blue (MB) can ameliorate behavioral, neurochemical, and neuropathological impairments in animal models of acute and chronic neurodegenerative disorders, but the underlying mechanism remains unclear. Myocyte enhancer factor 2 (MEF2D) is known to promote neuronal survival in several models, and several survival and death signals converge on MEF2D and regulate its activity. Here, we investigated the role of MEF2D in the neuroprotective effect of MB against glutamate-induced toxicity in HT22 neuronal cells. Our results showed that MB, event at less than 100 nM, improved the viability of HT22 cells exposed to 2 mM glutamate. MB attenuated the mitochondrial impairment and quenches the reactive oxygen species (ROS) induced by glutamate. Surprisingly, MB at 50–200 nM did not affect the Nrf2/HO-1 pathway, an important endogenous anti-oxidative system. Further study showed that MB increased the transcription and translation of MEF2D. In addition, MB upregulated the expression of mitochondrial NADH dehydrogenase 6 (ND6) in a MEF2D-dependent manner. Knockdown of MEF2D abolished both MB-medicated increase of ND6 and MB-induced neuroprotection against glutamate-induced toxicity. Moreover, we showed that MB promoted Akt function activity, suppressed GSK-3β activity, and increased MEF2D level in hippocampus of mice and HT22 cells. These findings for the first time demonstrate that MB protects HT22 neuronal cells against glutamate-induced cell death partially via the regulation of MEF2D-associated survival pathway.
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mef2d mediates the neuroprotective effect of methylene blue against glutamate induced oxidative damage in ht22 hippocampal cells
Molecular Neurobiology, 2017Co-Authors: Ziwei Chen, Wenming Li, Jingkao Chen, Xiaojuan Chao, Qian Yang, Rongbiao PiAbstract:Methylene blue (MB) can ameliorate behavioral, neurochemical, and neuropathological impairments in animal models of acute and chronic neurodegenerative disorders, but the underlying mechanism remains unclear. Myocyte enhancer factor 2 (MEF2D) is known to promote neuronal survival in several models, and several survival and death signals converge on MEF2D and regulate its activity. Here, we investigated the role of MEF2D in the neuroprotective effect of MB against glutamate-induced toxicity in HT22 neuronal cells. Our results showed that MB, event at less than 100 nM, improved the viability of HT22 cells exposed to 2 mM glutamate. MB attenuated the mitochondrial impairment and quenches the reactive oxygen species (ROS) induced by glutamate. Surprisingly, MB at 50–200 nM did not affect the Nrf2/HO-1 pathway, an important endogenous anti-oxidative system. Further study showed that MB increased the transcription and translation of MEF2D. In addition, MB upregulated the expression of mitochondrial NADH dehydrogenase 6 (ND6) in a MEF2D-dependent manner. Knockdown of MEF2D abolished both MB-medicated increase of ND6 and MB-induced neuroprotection against glutamate-induced toxicity. Moreover, we showed that MB promoted Akt function activity, suppressed GSK-3β activity, and increased MEF2D level in hippocampus of mice and HT22 cells. These findings for the first time demonstrate that MB protects HT22 neuronal cells against glutamate-induced cell death partially via the regulation of MEF2D-associated survival pathway.
Douglas C Wallace - One of the best experts on this subject based on the ideXlab platform.
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use of transmitochondrial cybrids to assign a complex i defect to the mitochondrial dna encoded nadh dehydrogenase subunit 6 gene mutation at nucleotide pair 14459 that causes leber hereditary optic neuropathy and dystonia
Molecular and Cellular Biology, 1996Co-Authors: Albert S Jun, Ian A Trounce, Michael D Brown, John M Shoffner, Douglas C WallaceAbstract:A heteroplasmic G-to-A transition at nucleotide pair (np) 14459 within the mitochondrial DNA (mtDNA)-encoded NADH dehydrogenase subunit 6 (ND6) gene has been identified as the cause of Leber hereditary optic neuropathy (LHON) and/or pediatric-onset dystonia in three unrelated families. This ND6 np 14459 mutation changes a moderately conserved alanine to a valine at amino acid position 72 of the ND6 protein. Enzymologic analysis of mitochondrial NADH dehydrogenase (complex I) with submitochondrial particles isolated from Epstein-Barr virus-transformed lymphoblasts revealed a 60% reduction (P < 0.005) of complex I-specific activity in patient cell lines compared with controls, with no differences in enzymatic activity for complexes II plus III, III and IV. This biochemical defect was assigned to the ND6 np 14459 mutation by using transmitochondrial cybrids in which patient Epstein-Barr virus-transformed lymphoblast cell lines were enucleated and the cytoplasts were fused to a mtDNA-deficient (p 0) lymphoblastoid recipient cell line. Cybrids harboring the np 14459 mutation exhibited a 39% reduction (p < 0.02) in complex I-specific activity relative to wild-type cybrid lines but normal activity for the other complexes. Kinetic analysis of the np 14459 mutant complex I revealed that the Vmax of the enzyme was reduced while the Km remained the same as that of wild type. Furthermore, specific activity was inhibited by increasing concentrations of the reduced coenzyme Q analog decylubiquinol. These observations suggest that the np 14459 mutation may alter the coenzyme Q-binding site of complex I.
Zissis Mamuris - One of the best experts on this subject based on the ideXlab platform.
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positive selection and precipitation effects on the mitochondrial nadh dehydrogenase subunit 6 gene in brown hares lepus europaeus under a phylogeographic perspective
PLOS ONE, 2019Co-Authors: Milomir Stefanovic, Mihajla Djan, Nevena Velickovic, Dejan Beukovic, Vukan Lavadinovic, Chavdar Dinev Zhelev, Yasin Demirbas, Ladislav Paule, Csongor I Gedeon, Zissis MamurisAbstract:Previous studies in hares and jackrabbits have indicated that positive selection has shaped the genetic diversity of mitochondrial genes involved in oxidative phosphorylation, which may affect cellular energy production and cause regional adaptation to different environmental (climatic) pressures. In the present study, we sequenced the NADH dehydrogenase subunit 6 (MT-ND6) gene of 267 brown hares (L. europaeus) from Europe and Asia Minor and tested for positive selection and adaptations acting on amino acid sequences (protein variants). Molecular diversity indices and spatial clustering were assessed by DnaSP, Network, and Geneland, while the presence of selection signals was tested by codeml in PAML, and by using the Datamonkey Adaptive Evolution web server. The SPSS software was used to run multinomial regression models to test for possible effects of climate parameters on the currently obtained protein variants. Fifty-eight haplotypes were revealed with a haplotype diversity of 0.817, coding for 17 different protein variants. The MT-ND6 phylogeographic pattern as determined by the nucleotide sequences followed the earlier found model based on the neutrally evolving D-loop sequences, and reflected the earlier found phylogeographic Late Pleistocene scenario. Based on several selection tests, only one codon position consistently proved to be under positive selection. It did occur exclusively in the evolutionarily younger hares from Europe and it gave rise to several protein variants from the southeastern and south-central Balkans. The occurrence of several of those variants was significantly favored under certain precipitation conditions, as proved by our multinomial regression models. Possibly, the great altitudinal variation in the Balkans may have lead to bigger changes in precipitation across that region and this may have imposed an evolutionarily novel selective pressure on the protein variants and could have led to regional adaptation.
Qian Yang - One of the best experts on this subject based on the ideXlab platform.
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mef2d mediates the neuroprotective effect of methylene blue against glutamate induced oxidative damage in ht22 hippocampal cells
Molecular Neurobiology, 2017Co-Authors: Ziwei Chen, Wenming Li, Jingkao Chen, Xiaojuan Chao, Qian Yang, Rongbiao PiAbstract:Methylene blue (MB) can ameliorate behavioral, neurochemical, and neuropathological impairments in animal models of acute and chronic neurodegenerative disorders, but the underlying mechanism remains unclear. Myocyte enhancer factor 2 (MEF2D) is known to promote neuronal survival in several models, and several survival and death signals converge on MEF2D and regulate its activity. Here, we investigated the role of MEF2D in the neuroprotective effect of MB against glutamate-induced toxicity in HT22 neuronal cells. Our results showed that MB, event at less than 100 nM, improved the viability of HT22 cells exposed to 2 mM glutamate. MB attenuated the mitochondrial impairment and quenches the reactive oxygen species (ROS) induced by glutamate. Surprisingly, MB at 50–200 nM did not affect the Nrf2/HO-1 pathway, an important endogenous anti-oxidative system. Further study showed that MB increased the transcription and translation of MEF2D. In addition, MB upregulated the expression of mitochondrial NADH dehydrogenase 6 (ND6) in a MEF2D-dependent manner. Knockdown of MEF2D abolished both MB-medicated increase of ND6 and MB-induced neuroprotection against glutamate-induced toxicity. Moreover, we showed that MB promoted Akt function activity, suppressed GSK-3β activity, and increased MEF2D level in hippocampus of mice and HT22 cells. These findings for the first time demonstrate that MB protects HT22 neuronal cells against glutamate-induced cell death partially via the regulation of MEF2D-associated survival pathway.
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mef2d mediates the neuroprotective effect of methylene blue against glutamate induced oxidative damage in ht22 hippocampal cells
Molecular Neurobiology, 2017Co-Authors: Ziwei Chen, Wenming Li, Jingkao Chen, Xiaojuan Chao, Qian Yang, Rongbiao PiAbstract:Methylene blue (MB) can ameliorate behavioral, neurochemical, and neuropathological impairments in animal models of acute and chronic neurodegenerative disorders, but the underlying mechanism remains unclear. Myocyte enhancer factor 2 (MEF2D) is known to promote neuronal survival in several models, and several survival and death signals converge on MEF2D and regulate its activity. Here, we investigated the role of MEF2D in the neuroprotective effect of MB against glutamate-induced toxicity in HT22 neuronal cells. Our results showed that MB, event at less than 100 nM, improved the viability of HT22 cells exposed to 2 mM glutamate. MB attenuated the mitochondrial impairment and quenches the reactive oxygen species (ROS) induced by glutamate. Surprisingly, MB at 50–200 nM did not affect the Nrf2/HO-1 pathway, an important endogenous anti-oxidative system. Further study showed that MB increased the transcription and translation of MEF2D. In addition, MB upregulated the expression of mitochondrial NADH dehydrogenase 6 (ND6) in a MEF2D-dependent manner. Knockdown of MEF2D abolished both MB-medicated increase of ND6 and MB-induced neuroprotection against glutamate-induced toxicity. Moreover, we showed that MB promoted Akt function activity, suppressed GSK-3β activity, and increased MEF2D level in hippocampus of mice and HT22 cells. These findings for the first time demonstrate that MB protects HT22 neuronal cells against glutamate-induced cell death partially via the regulation of MEF2D-associated survival pathway.
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direct regulation of complex i by mitochondrial mef2d is disrupted in a mouse model of parkinson disease and in human patients
Journal of Clinical Investigation, 2011Co-Authors: Qian Yang, Kennie R Shepherd, Gary W Miller, Yoland Smith, Claudia M. TestaAbstract:The transcription factors in the myocyte enhancer factor 2 (MEF2) family play important roles in cell survival by regulating nuclear gene expression. Here, we report that MEF2D is present in rodent neuronal mitochondria, where it can regulate the expression of a gene encoded within mitochondrial DNA (mtDNA). Immunocytochemical, immunoelectron microscopic, and biochemical analyses of rodent neuronal cells showed that a portion of MEF2D was targeted to mitochondria via an N-terminal motif and the chaperone protein mitochondrial heat shock protein 70 (mtHsp70). MEF2D bound to a MEF2 consensus site in the region of the mtDNA that contained the gene NADH dehydrogenase 6 (ND6), which encodes an essential component of the complex I enzyme of the oxidative phosphorylation system; MEF2D binding induced ND6 transcription. Blocking MEF2D function specifically in mitochondria decreased complex I activity, increased cellular H2O2 level, reduced ATP production, and sensitized neurons to stress-induced death. Toxins known to affect complex I preferentially disrupted MEF2D function in a mouse model of Parkinson disease (PD). In addition, mitochondrial MEF2D and ND6 levels were decreased in postmortem brain samples of patients with PD compared with age-matched controls. Thus, direct regulation of complex I by mitochondrial MEF2D underlies its neuroprotective effects, and dysregulation of this pathway may contribute to PD.
Ziwei Chen - One of the best experts on this subject based on the ideXlab platform.
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mef2d mediates the neuroprotective effect of methylene blue against glutamate induced oxidative damage in ht22 hippocampal cells
Molecular Neurobiology, 2017Co-Authors: Ziwei Chen, Wenming Li, Jingkao Chen, Xiaojuan Chao, Qian Yang, Rongbiao PiAbstract:Methylene blue (MB) can ameliorate behavioral, neurochemical, and neuropathological impairments in animal models of acute and chronic neurodegenerative disorders, but the underlying mechanism remains unclear. Myocyte enhancer factor 2 (MEF2D) is known to promote neuronal survival in several models, and several survival and death signals converge on MEF2D and regulate its activity. Here, we investigated the role of MEF2D in the neuroprotective effect of MB against glutamate-induced toxicity in HT22 neuronal cells. Our results showed that MB, event at less than 100 nM, improved the viability of HT22 cells exposed to 2 mM glutamate. MB attenuated the mitochondrial impairment and quenches the reactive oxygen species (ROS) induced by glutamate. Surprisingly, MB at 50–200 nM did not affect the Nrf2/HO-1 pathway, an important endogenous anti-oxidative system. Further study showed that MB increased the transcription and translation of MEF2D. In addition, MB upregulated the expression of mitochondrial NADH dehydrogenase 6 (ND6) in a MEF2D-dependent manner. Knockdown of MEF2D abolished both MB-medicated increase of ND6 and MB-induced neuroprotection against glutamate-induced toxicity. Moreover, we showed that MB promoted Akt function activity, suppressed GSK-3β activity, and increased MEF2D level in hippocampus of mice and HT22 cells. These findings for the first time demonstrate that MB protects HT22 neuronal cells against glutamate-induced cell death partially via the regulation of MEF2D-associated survival pathway.
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mef2d mediates the neuroprotective effect of methylene blue against glutamate induced oxidative damage in ht22 hippocampal cells
Molecular Neurobiology, 2017Co-Authors: Ziwei Chen, Wenming Li, Jingkao Chen, Xiaojuan Chao, Qian Yang, Rongbiao PiAbstract:Methylene blue (MB) can ameliorate behavioral, neurochemical, and neuropathological impairments in animal models of acute and chronic neurodegenerative disorders, but the underlying mechanism remains unclear. Myocyte enhancer factor 2 (MEF2D) is known to promote neuronal survival in several models, and several survival and death signals converge on MEF2D and regulate its activity. Here, we investigated the role of MEF2D in the neuroprotective effect of MB against glutamate-induced toxicity in HT22 neuronal cells. Our results showed that MB, event at less than 100 nM, improved the viability of HT22 cells exposed to 2 mM glutamate. MB attenuated the mitochondrial impairment and quenches the reactive oxygen species (ROS) induced by glutamate. Surprisingly, MB at 50–200 nM did not affect the Nrf2/HO-1 pathway, an important endogenous anti-oxidative system. Further study showed that MB increased the transcription and translation of MEF2D. In addition, MB upregulated the expression of mitochondrial NADH dehydrogenase 6 (ND6) in a MEF2D-dependent manner. Knockdown of MEF2D abolished both MB-medicated increase of ND6 and MB-induced neuroprotection against glutamate-induced toxicity. Moreover, we showed that MB promoted Akt function activity, suppressed GSK-3β activity, and increased MEF2D level in hippocampus of mice and HT22 cells. These findings for the first time demonstrate that MB protects HT22 neuronal cells against glutamate-induced cell death partially via the regulation of MEF2D-associated survival pathway.