The role of post-translational modifications in driving abnormal cardiovascular complications at high altitude

Hou, Jing; Wen, Xudong; Long, Ping; Xiong, Shiqiang; Liu, Hanxiong; Cai, Lin; Deng, Hongbin; Zhang, Zhen

doi:10.3389/fcvm.2022.886300

Cited by 12 publications

(11 citation statements)

References 131 publications

(133 reference statements)

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“…40 Furthermore, protein lactylation has been associated with the regulation of environmental stress responses and organismal adaptation. 41 In plant physiology, a study has established a correlation between lactate and lactylation with the physiological response of maize root systems to drought stress. 42 Similarly, in animals enduring prolonged environmental stress, genes regulating lipid synthesis are downregulated, while those related to gluconeogenesis, 43 fatty acid oxidation, 43 and peroxisome proliferatoractivated receptor A (PPAR-A) target gene associated with lipolysis are upregulated.…”

Section: ■ Discussionmentioning

confidence: 99%

Protein Lactylation Profiles Provide Insights into Molecular Mechanisms Underlying Metabolism in Yak

Wu,

Chai,

Cai

et al. 2024

J. Agric. Food Chem.

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Protein lysine lactylation, a recently discovered post-translational modification (PTM), is prevalent across tissues and cells of diverse species, serving as a regulator of glycolytic flux and biological metabolism. The yak (Bos grunniens), a species that has inhabited the Qinghai−Tibetan Plateau for millennia, has evolved intricate adaptive mechanisms to cope with the region's unique geographical and climatic conditions, exhibiting remarkable energy utilization and metabolic efficiency. Nonetheless, the specific landscape of lysine lactylation in yaks remains poorly understood. Herein, we present the first comprehensive lactylome profile of the yak, effectively identifying 421, 308, and 650 lactylated proteins in the heart, muscles, and liver, respectively. These lactylated proteins are involved in glycolysis/gluconeogenesis, the tricarboxylic acid cycle, oxidative phosphorylation, and metabolic process encompassing carbohydrates, lipids, and proteins during both anaerobic and aerobic glucose bio-oxidation, implying their crucial role in material and energy metabolism, as well as in maintaining homeostasis in yaks.

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Section: ■ Discussionmentioning

confidence: 99%

Protein Lactylation Profiles Provide Insights into Molecular Mechanisms Underlying Metabolism in Yak

Wu,

Chai,

Cai

et al. 2024

J. Agric. Food Chem.

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“…I Na alterations have been implicated in HF. A HF study conducted on mice missing the expression of the Muscle Lim Protein (MLP) demonstrated a decreased of I Na density by post-translational reduction ( 35 , 36 ). This I Na reduction decreased the electrical conduction, favored re-entry, and contributed to inefficient synchronized conduction.…”

Section: Electrical Remodelingmentioning

confidence: 99%

Ion channel trafficking implications in heart failure

Reisqs,

Qu,

Boutjdir

2024

Front. Cardiovasc. Med.

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Heart failure (HF) is recognized as an epidemic in the contemporary world, impacting around 1%–2% of the adult population and affecting around 6 million Americans. HF remains a major cause of mortality, morbidity, and poor quality of life. Several therapies are used to treat HF and improve the survival of patients; however, despite these substantial improvements in treating HF, the incidence of HF is increasing rapidly, posing a significant burden to human health. The total cost of care for HF is USD 69.8 billion in 2023, warranting a better understanding of the mechanisms involved in HF. Among the most serious manifestations associated with HF is arrhythmia due to the electrophysiological changes within the cardiomyocyte. Among these electrophysiological changes, disruptions in sodium and potassium currents’ function and trafficking, as well as calcium handling, all of which impact arrhythmia in HF. The mechanisms responsible for the trafficking, anchoring, organization, and recycling of ion channels at the plasma membrane seem to be significant contributors to ion channels dysfunction in HF. Variants, microtubule alterations, or disturbances of anchoring proteins lead to ion channel trafficking defects and the alteration of the cardiomyocyte's electrophysiology. Understanding the mechanisms of ion channels trafficking could provide new therapeutic approaches for the treatment of HF. This review provides an overview of the recent advances in ion channel trafficking in HF.

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“…One potential tool for studying how proteins are perturbed in the presence of PSNPs is lysine methylation. Methylation is a crucial post-translational modification in regulating diverse cellular processes and orchestrating complex biological functions. , Biologically, methylation is performed by a family of enzymes known as lysine methyltransferases . However, methylation can also be performed reductively using formaldehyde under mild conditions that do not alter the protein’s structure .…”

Section: Introductionmentioning

confidence: 99%

Exploring Residue-Level Interactions between the Biofilm-Driving R2ab Protein and Polystyrene Nanoparticles

Somarathne,

Misra,

Kariyawasam

et al. 2024

Langmuir

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In biological systems, proteins can bind to nanoparticles to form a "corona" of adsorbed molecules. The nanoparticle corona is of significant interest because it impacts an organism's response to a nanomaterial. Understanding the corona requires knowledge of protein structure, orientation, and dynamics at the surface. A residue-level mapping of protein behavior on nanoparticle surfaces is needed, but this mapping is difficult to obtain with traditional approaches. Here, we have investigated the interaction between R2ab and polystyrene nanoparticles (PSNPs) at the level of individual residues. R2ab is a bacterial surface protein from Staphylococcus epidermidis and is known to interact strongly with polystyrene, leading to biofilm formation. We have used mass spectrometry after lysine methylation and hydrogen−deuterium exchange (HDX) NMR spectroscopy to understand how the R2ab protein interacts with PSNPs of different sizes. Lysine methylation experiments reveal subtle but statistically significant changes in methylation patterns in the presence of PSNPs, indicating altered protein surface accessibility. HDX rates become slower overall in the presence of PSNPs. However, some regions of the R2ab protein exhibit faster than average exchange rates in the presence of PSNPs, while others are slower than the average behavior, suggesting conformational changes upon binding. HDX rates and methylation ratios support a recently proposed "adsorbotope" model for PSNPs, wherein adsorbed proteins consist of unfolded anchor points interspersed with partially structured regions. Our data also highlight the challenges of characterizing complex protein-nanoparticle interactions using these techniques, such as fast exchange rates. While providing insights into how R2ab adsorbs onto PSNP surfaces, this research emphasizes the need for advanced methods to comprehend residue-level interactions in the nanoparticle corona.

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The role of post-translational modifications in driving abnormal cardiovascular complications at high altitude

Cited by 12 publications

References 131 publications

Protein Lactylation Profiles Provide Insights into Molecular Mechanisms Underlying Metabolism in Yak

Protein Lactylation Profiles Provide Insights into Molecular Mechanisms Underlying Metabolism in Yak

Ion channel trafficking implications in heart failure

Exploring Residue-Level Interactions between the Biofilm-Driving R2ab Protein and Polystyrene Nanoparticles

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