Fatty Acid Biosynthesis Inhibition Increases Reduction Potential in Neuronal Cells under Hypoxia

Brose, Stephen A.; Golovko, Svetlana A.; Golovko, Mikhail Y.

doi:10.3389/fnins.2016.00546

Cited by 15 publications

(22 citation statements)

References 51 publications

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“…The synthetic precursors of glutaric acid were malonyl-CoA and acetyl-CoA. Partially impairing the fatty acid pathway and tricarboxylic acid cycle by microaerobic condition could well drive acetyl-CoA and malonyl-CoA toward glutarate production while sustaining certain cell growth and metabolism requirements (Brose, Golovko, & Golovko, 2016;Zhao, Li, & Deng, 2018). At the same time, the production of acetic acid was also affected by dissolved oxygen during the fermentation process and relatively high in microaerobic condition (Fig.…”

Section: Discussionmentioning

confidence: 98%

Improving glutarate production in Escherichia coli by enhancing the CoA precursors

Zhao

Zhou

Sui

et al. 2020

Preprint

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Glutarate is an attractive C5 platform chemical having wide application in nylon and plasticizer. However, microbial glutarate is mainly accumulated in the degradation of lysine and other methods were rarely explored for producing the glutarate from glucose directly. Here, we utilized a reversed adipic acid degradation pathway (RADP) and improved the glutarate production by increasing the precursors (malonyl-CoA and acetyl-CoA) based on the previously studied strain Bgl4146. Specifically, the conversion system of intracellular acetyl-CoA to malonyl-CoA was firstly constructed and optimized to balance acetyl-CoA synthase and acetyl-CoA carboxylase under different dissolved oxygen, enhancing the glutarate production from 0.09 g/L to 0.49 g/L. Then, modulating CoA balance by monitoring the expression of acetate kinase and pyruvate dehydrogenase resulting in a rise in glutarate titer up to 0.70 g/L. Finally, the optimized strain Bgl51464 was able to produce 7.97 g/L glutarate in a 5-L bioreactor. This strategy was described here, which could lay a certain foundation for the development of effective CoA balance to produce industrially high value-added chemicals.

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Section: Discussionmentioning

confidence: 98%

Improving glutarate production in Escherichia coli by enhancing the CoA precursors

Zhao

Zhou

Sui

et al. 2020

Preprint

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“…Oxidative phosphorylation is a process strongly affected by reduced oxygen supply and is downregulated following hypoxia exposure, since cells upregulate components of alternative energy production, including glycolytic enzymes and glucose transporters to compensate for the loss of energy [ 53 ]. In addition, increased fatty acid biosynthesis in human neuroblastoma cells has been reported in response to hypoxia, possibly to counteract brain lactoacidosis and the loss of reduction potential [ 54 ].…”

Section: Overlapping Molecular Pathways Of Hypoxic and Chemical Comentioning

confidence: 99%

A Rationale for Hypoxic and Chemical Conditioning in Huntington’s Disease

Burtscher

Maglione

Pardo

et al. 2021

IJMS

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Neurodegenerative diseases are characterized by adverse cellular environments and pathological alterations causing neurodegeneration in distinct brain regions. This development is triggered or facilitated by conditions such as hypoxia, ischemia or inflammation and is associated with disruptions of fundamental cellular functions, including metabolic and ion homeostasis. Targeting intracellular downstream consequences to specifically reverse these pathological changes proved difficult to translate to clinical settings. Here, we discuss the potential of more holistic approaches with the purpose to re-establish a healthy cellular environment and to promote cellular resilience. We review the involvement of important molecular pathways (e.g., the sphingosine, δ-opioid receptor or N-Methyl-D-aspartate (NMDA) receptor pathways) in neuroprotective hypoxic conditioning effects and how these pathways can be targeted for chemical conditioning. Despite the present scarcity of knowledge on the efficacy of such approaches in neurodegeneration, the specific characteristics of Huntington’s disease may make it particularly amenable for such conditioning techniques. Not only do classical features of neurodegenerative diseases like mitochondrial dysfunction, oxidative stress and inflammation support this assumption, but also specific Huntington’s disease characteristics: a relatively young age of neurodegeneration, molecular overlap of related pathologies with hypoxic adaptations and sensitivity to brain hypoxia. The aim of this review is to discuss several molecular pathways in relation to hypoxic adaptations that have potential as drug targets in neurodegenerative diseases. We will extract the relevance for Huntington’s disease from this knowledge base.

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“…SREBP-1c, a SREBP family member, is involved in triglyceride and fatty acid synthesis predominantly in the liver, which leads to fat accumulation ( Shimano et al, 1997 ; Shimomura et al, 1998 ). Additionally, p53 has been implicated in inhibiting FAS through repression of NADPH production, a critical energy source utilized during FAS ( Brose et al, 2016 ). p53 can inhibit NADPH production through negative transcriptional regulation of malic enzyme 1 and 2 (ME1 and 2) ( Jiang et al, 2013 ).…”

Section: Lipid Metabolismmentioning

confidence: 99%

The p53 Family: A Role in Lipid and Iron Metabolism

Laubach

Zhang

Chen

2021

Front. Cell Dev. Biol.

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The p53 family of tumor suppressors, which includes p53, p63, and p73, has a critical role in many biological processes, such as cell cycle arrest, apoptosis, and differentiation. In addition to tumor suppression, the p53 family proteins also participate in development, multiciliogenesis, and fertility, indicating these proteins have diverse roles. In this review, we strive to cover the relevant studies that demonstrate the roles of p53, p63, and p73 in lipid and iron metabolism.

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Fatty Acid Biosynthesis Inhibition Increases Reduction Potential in Neuronal Cells under Hypoxia

Cited by 15 publications

References 51 publications

Improving glutarate production in Escherichia coli by enhancing the CoA precursors

Improving glutarate production in Escherichia coli by enhancing the CoA precursors

A Rationale for Hypoxic and Chemical Conditioning in Huntington’s Disease

The p53 Family: A Role in Lipid and Iron Metabolism

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