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Inhibitory effect of homocysteine on rat neural stem cell growth in vitro is associated with reduced protein levels and enzymatic activities of aconitase and respiratory complex III.
J Bioenerg Biomembr. 2017 Apr; 49(2):131-138.JB

Abstract

Increased blood plasma concentration of the sulphur amino acid homocysteine (Hcy) is considered as an independent risk factor of the neurodegenerative diseases. However, the detailed molecular mechanisms by which Hcy leads to neurotoxicity have yet to be clarified. Recent research has suggested that neurotoxicity of Hcy may involve negative regulation of neural stem cell (NSC) proliferation. In the current study, primary NSCs were isolated from neonatal rat brain hippocampus and the inhibition in cell growth was observed after exposure to l50 μM and 500 μM L-Hcy. The changes in protein expression were monitored with densitometric 2D-gel electrophoresis coupled with MALDI-TOF mass spectrometry. Proteomic analysis revealed that the expression levels of two mitochondrial proteins, cytochrome bc1 complex2 (UQCRC2, the major component of electron transport chain complex III) and aconitase (an enzyme involved in the tricarboxylic acid cycle), were decreased in Hcy treatment group, compared to control group. Protein expression was further verified by Western blot, and their enzymatic activities were also down-regulated in NSCs after Hcy treatment. Restoration of aconitase and UQCRC2 protein levels using their expression vectors could partly rescue the cell viability inhibition caused by Hcy. Moreover, Hcy caused the increase in the intracellular levels of reactive oxygen species (ROS) and the decrease in ATP content, which are known to play important roles in the cellular stress response of the cell growth. Altogether, the results suggest that the decreased expression and enzymatic activities of the mitochondrial proteins may be possible causes of the overproduction of ROS and depletion of ATP. The inhibition in cell growth at the end of Hcy treatment was probably due to the changes in protein expression and mitochondrial dysfunction in vitro cultures of NSCs.

Authors+Show Affiliations

Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, 300070, China.Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, 300070, China.Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, 300070, China.Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, 300070, China.Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, 300070, China. huangguowei@tmu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27914013

Citation

Zhang, Xu-Mei, et al. "Inhibitory Effect of Homocysteine On Rat Neural Stem Cell Growth in Vitro Is Associated With Reduced Protein Levels and Enzymatic Activities of Aconitase and Respiratory Complex III." Journal of Bioenergetics and Biomembranes, vol. 49, no. 2, 2017, pp. 131-138.
Zhang XM, Zhao YQ, Yan H, et al. Inhibitory effect of homocysteine on rat neural stem cell growth in vitro is associated with reduced protein levels and enzymatic activities of aconitase and respiratory complex III. J Bioenerg Biomembr. 2017;49(2):131-138.
Zhang, X. M., Zhao, Y. Q., Yan, H., Liu, H., & Huang, G. W. (2017). Inhibitory effect of homocysteine on rat neural stem cell growth in vitro is associated with reduced protein levels and enzymatic activities of aconitase and respiratory complex III. Journal of Bioenergetics and Biomembranes, 49(2), 131-138. https://doi.org/10.1007/s10863-016-9688-2
Zhang XM, et al. Inhibitory Effect of Homocysteine On Rat Neural Stem Cell Growth in Vitro Is Associated With Reduced Protein Levels and Enzymatic Activities of Aconitase and Respiratory Complex III. J Bioenerg Biomembr. 2017;49(2):131-138. PubMed PMID: 27914013.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibitory effect of homocysteine on rat neural stem cell growth in vitro is associated with reduced protein levels and enzymatic activities of aconitase and respiratory complex III. AU - Zhang,Xu-Mei, AU - Zhao,Ya-Qian, AU - Yan,Hai, AU - Liu,Huan, AU - Huang,Guo-Wei, Y1 - 2016/12/02/ PY - 2016/05/18/received PY - 2016/11/07/accepted PY - 2016/12/4/pubmed PY - 2017/12/7/medline PY - 2016/12/4/entrez KW - ATP KW - Aconitase KW - Cytochrome bc1 complex2 KW - Homocysteine KW - Neural stem cell KW - ROS SP - 131 EP - 138 JF - Journal of bioenergetics and biomembranes JO - J. Bioenerg. Biomembr. VL - 49 IS - 2 N2 - Increased blood plasma concentration of the sulphur amino acid homocysteine (Hcy) is considered as an independent risk factor of the neurodegenerative diseases. However, the detailed molecular mechanisms by which Hcy leads to neurotoxicity have yet to be clarified. Recent research has suggested that neurotoxicity of Hcy may involve negative regulation of neural stem cell (NSC) proliferation. In the current study, primary NSCs were isolated from neonatal rat brain hippocampus and the inhibition in cell growth was observed after exposure to l50 μM and 500 μM L-Hcy. The changes in protein expression were monitored with densitometric 2D-gel electrophoresis coupled with MALDI-TOF mass spectrometry. Proteomic analysis revealed that the expression levels of two mitochondrial proteins, cytochrome bc1 complex2 (UQCRC2, the major component of electron transport chain complex III) and aconitase (an enzyme involved in the tricarboxylic acid cycle), were decreased in Hcy treatment group, compared to control group. Protein expression was further verified by Western blot, and their enzymatic activities were also down-regulated in NSCs after Hcy treatment. Restoration of aconitase and UQCRC2 protein levels using their expression vectors could partly rescue the cell viability inhibition caused by Hcy. Moreover, Hcy caused the increase in the intracellular levels of reactive oxygen species (ROS) and the decrease in ATP content, which are known to play important roles in the cellular stress response of the cell growth. Altogether, the results suggest that the decreased expression and enzymatic activities of the mitochondrial proteins may be possible causes of the overproduction of ROS and depletion of ATP. The inhibition in cell growth at the end of Hcy treatment was probably due to the changes in protein expression and mitochondrial dysfunction in vitro cultures of NSCs. SN - 1573-6881 UR - https://www.unboundmedicine.com/medline/citation/27914013/Inhibitory_effect_of_homocysteine_on_rat_neural_stem_cell_growth_in_vitro_is_associated_with_reduced_protein_levels_and_enzymatic_activities_of_aconitase_and_respiratory_complex_III_ L2 - https://doi.org/10.1007/s10863-016-9688-2 DB - PRIME DP - Unbound Medicine ER -