Protein-protein interactions involving enzymes of the mammalian methionine and homocysteine metabolism

Portillo, Francisco García‐del; Vázquez, Jesús; Pajares, Marı́a A.

doi:10.1016/j.biochi.2020.02.015

Cited by 32 publications

(26 citation statements)

References 130 publications

(290 reference statements)

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“…As a precursor of S ‐adenosylmethionine (SAM), a universal methyl donor, a high level of Hcy can lead to the increase in SAM level, which accordingly upregulates the activity of DNMTs using the substrate of DNMT [ 24 , 25 ]. Our previous study showed that DNA methylation can contribute to the development of diseases such as cardiovascular and liver diseases caused by Hcy [ 15 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

Homocysteine induces podocyte apoptosis by regulating miR‐1929‐5p expression through c‐Myc, DNMT1 and EZH2

Xie

Ding

et al. 2021

Molecular Oncology

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Chronic kidney disease (CKD) is a common and complex disease in kidneys which has been associated with an increased risk of renal cell carcinoma. Elevated homocysteine (Hcy) levels are known to influence the development and progression of CKD by regulating podocyte injury and apoptosis. To investigate the molecular mechanisms triggered in podocytes by Hcy, we used cbs+/− mice and observed that higher Hcy levels increased the apoptosis rate of podocytes with accompanying glomerular damage. Hcy‐induced podocyte injury and apoptosis in cbs+/− mice was regulated by inhibition of microRNA (miR)‐1929‐5p expression. Overexpression of miR‐1929‐5p in podocytes inhibited apoptosis by upregulating Bcl‐2. Furthermore, the expression of miR‐1929‐5p was regulated by epigenetic modifications of its promoter. Hcy upregulated DNA methyltransferase 1 (DNMT1) and enhancer of zeste homolog 2 (EZH2) levels, resulting in increased DNA methylation and H3K27me3 levels on the miR‐1929‐5p promoter. Additionally, we observed that c‐Myc recruited DNMT1 and EZH2 to the miR‐1929‐5p promoter and suppressed the expression of miR‐1929‐5p. In summary, we demonstrated that Hcy promotes podocyte apoptosis through the regulation of the epigenetic modifiers DNMT1 and EZH2, which are recruited by c‐Myc to the promoter of miR‐1929‐5p to silence miR‐1929‐5p expression.

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Section: Discussionmentioning

confidence: 99%

Homocysteine induces podocyte apoptosis by regulating miR‐1929‐5p expression through c‐Myc, DNMT1 and EZH2

Xie

Ding

et al. 2021

Molecular Oncology

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“…Weak transient interactions associate and dissociate continuously (e.g., high dissociation rate), like most receptor–receptor interactions ( Perkins et al, 2010 ; Acuner Ozbabacan et al, 2011 ). The characterization of these interactions in their native environment has been challenging compared with strong and high-affinity interactions that can be captured by most available biochemical approaches ( Xing et al, 2016 ; Titeca et al, 2019 ; Portillo et al, 2020 ). Different methods are available to investigate the interaction of hydrophobic proteins, such as membrane proteins ( Snider et al, 2015 ).…”

Section: Protein–protein Interactions At the Plasma Membrane: Detection Methodsmentioning

confidence: 99%

Regulation of membrane NMDA receptors by dynamics and protein interactions

Petit‐Pedrol

Groc

2020

Journal of Cell Biology

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Understanding neurotransmitter system crosstalk in the brain is a major challenge in neurobiology. Several intracellular and genomic cascades have been identified in this crosstalk. However, the discovery that neurotransmitter receptors are highly diffusive in the plasma membrane of neurons, where they form heterocomplexes with other proteins, has profoundly changed our view of neurotransmitter signaling. Here, we review new insights into neurotransmitter crosstalk at the plasma membrane. We focus on the membrane organization and interactome of the ionotropic glutamate N-methyl-D-aspartate receptor (NMDAR) that plays a central role in excitatory synaptic and network physiology and is involved in the etiology of several major neuropsychiatric disorders. The nanoscale organization and dynamics of NMDAR is a key regulatory process for glutamate synapse transmission, plasticity, and crosstalk with other neurotransmitter systems, such as the monoaminergic ones. The plasma membrane appears to be a prime regulatory compartment for spatial and temporal crosstalk between neurotransmitter systems in the healthy and diseased brain. Understanding the molecular mechanisms regulating membrane neurotransmitter receptor crosstalk will likely open research avenues for innovative therapeutical strategies.

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“…Homocysteine (Hcy), a sulfur amino acid, is generated during the metabolism of methionine 93 . Hyperhomocysteinemia (HHcy) is an independent risk factor associated with cardiovascular complications such as MI 94 .…”

Section: Targeting Er Stress By H2s In Different Cardiac Disordersmentioning

confidence: 99%

“…Homocysteine (Hcy), a sulfur amino acid, is generated during the metabolism of methionine. 93 Hyperhomocysteinemia (HHcy) is an independent risk factor associated with cardiovascular complications such as MI. 94 HHcy can induce myocardial oxidative stress, 95 hypomethylation, 96 and ER stress-mediated apoptosis.…”

Section: Targeting Er Stress By H 2 S In Hyperhomocysteinemia-induced...mentioning

confidence: 99%

The cardioprotective effects of hydrogen sulfide by targeting endoplasmic reticulum stress and the Nrf2 signaling pathway: A review

2021

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Cardiac diseases are emerging due to lifestyle, urbanization, and the accelerated aging process. Oxidative stress has been associated with cardiac injury progression through interference with antioxidant strategies and endoplasmic reticulum (ER) function. Hydrogen sulfide (H 2 S) is generated endogenously from L-cysteine in various tissues including heart tissue. Pharmacological evaluation of H 2 S has suggested a potential role for H 2 S against diabetic cardiomyopathy, ischemia/reperfusion injury, myocardial infarction, and cardiotoxicity.Nuclear factor E2-related factor 2 (Nrf2) activity is crucial for cell survival in response to oxidative stress. H 2 S up-regulates Nrf2 expression and its related signaling pathway in myocytes. H 2 S also suppresses the expression and activity of ER stress-related proteins. H 2 S has been reported to improve various cardiac conditions through antioxidant and anti-ER stress-related activities.

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Protein-protein interactions involving enzymes of the mammalian methionine and homocysteine metabolism

Cited by 32 publications

References 130 publications

Homocysteine induces podocyte apoptosis by regulating miR‐1929‐5p expression through c‐Myc, DNMT1 and EZH2

Homocysteine induces podocyte apoptosis by regulating miR‐1929‐5p expression through c‐Myc, DNMT1 and EZH2

Regulation of membrane NMDA receptors by dynamics and protein interactions

The cardioprotective effects of hydrogen sulfide by targeting endoplasmic reticulum stress and the Nrf2 signaling pathway: A review

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