Role of lysophosphatidic acid in ion channel function and disease

Hernández-Araiza, Ileana; Morales‐Lázaro, Sara L.; Canul-Sánchez, Jesús Aldair; Islas, León D; Rosenbaum, Tamara

doi:10.1152/jn.00226.2018

Cited by 22 publications

(16 citation statements)

References 114 publications

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“…There are six LPA-associated G protein-coupled receptors (GPCRs), LPA 1–6 or LPAR 1–6 , involved in autotaxin–LPA axis signaling [216,217]. LPA induces a variety of responses such as cell proliferation and migration and cytokine production via GPCR signaling and the effects on ion channels under normal and pathological conditions [218]. LPA plays an important physiological role in the functioning of the immune system.…”

Section: Lysophosphatidylcholine Turnovermentioning

confidence: 99%

An Updated Review of Lysophosphatidylcholine Metabolism in Human Diseases

Law

Chan

Marathe

et al. 2019

IJMS

533

379

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Lysophosphatidylcholine (LPC) is increasingly recognized as a key marker/factor positively associated with cardiovascular and neurodegenerative diseases. However, findings from recent clinical lipidomic studies of LPC have been controversial. A key issue is the complexity of the enzymatic cascade involved in LPC metabolism. Here, we address the coordination of these enzymes and the derangement that may disrupt LPC homeostasis, leading to metabolic disorders. LPC is mainly derived from the turnover of phosphatidylcholine (PC) in the circulation by phospholipase A2 (PLA2). In the presence of Acyl-CoA, lysophosphatidylcholine acyltransferase (LPCAT) converts LPC to PC, which rapidly gets recycled by the Lands cycle. However, overexpression or enhanced activity of PLA2 increases the LPC content in modified low-density lipoprotein (LDL) and oxidized LDL, which play significant roles in the development of atherosclerotic plaques and endothelial dysfunction. The intracellular enzyme LPCAT cannot directly remove LPC from circulation. Hydrolysis of LPC by autotaxin, an enzyme with lysophospholipase D activity, generates lysophosphatidic acid, which is highly associated with cancers. Although enzymes with lysophospholipase A1 activity could theoretically degrade LPC into harmless metabolites, they have not been found in the circulation. In conclusion, understanding enzyme kinetics and LPC metabolism may help identify novel therapeutic targets in LPC-associated diseases.

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Section: Lysophosphatidylcholine Turnovermentioning

confidence: 99%

An Updated Review of Lysophosphatidylcholine Metabolism in Human Diseases

Law

Chan

Marathe

et al. 2019

IJMS

533

379

View full text Add to dashboard Cite

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“…LPA has been extensively linked to the generation of chronic neuropathic pain through its interactions with G protein-coupled receptors (GPCRs) [89][90][91][92] and to modulate the activity of several ion channels [93][94][95][96][97]. Regulation of the activity of TRPV1 by molecules of a lipidic nature has been explored, and it has been described that PIP 2 [98][99][100][101][102][103][104][105][106], polyunsaturated fatty acids (PUFAs) [107], monounsaturated fatty acids [108] and cholesterol [109][110][111] can modulate the activity of TRPV1, either directly or indirectly.…”

Section: Lysophosphatidic Acid: a Pain-producing Phospholipidmentioning

confidence: 99%

TRP ion channels: Proteins with conformational flexibility

et al. 2019

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Ion channels display conformational changes in response to binding of their agonists and antagonists. The study of the relationships between the structure and the function of these proteins has witnessed considerable advances in the last two decades using a combination of techniques, which include electrophysiology, optical approaches (i.e. patch clamp fluorometry, incorporation of non-canonic amino acids, etc.), molecular biology (mutations in different regions of ion channels to determine their role in function) and those that have permitted the resolution of their structures in detail (X-ray crystallography and cryo-electron microscopy). The possibility of making correlations among structural components and functional traits in ion channels has allowed for more refined conclusions on how these proteins work at the molecular level. With the cloning and description of the family of Transient Receptor Potential (TRP) channels, our understanding of several sensory-related processes has also greatly moved forward. The response of these proteins to several agonists, their regulation by signaling pathways as well as by protein-protein and lipid-protein interactions and, in some cases, their biophysical characteristics have been studied thoroughly and, recently, with the resolution of their structures, the field has experienced a new boom. This review article focuses on the conformational changes in the pores, concentrating on some members of the TRP family of ion channels (TRPV and TRPA subfamilies) that result in changes in their single-channel conductances, a phenomenon that may lead to fine-tuning the electrical response to a given agonist in a cell.

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“…Therefore, dysfunction of ion channel expression and function can lead to vascular diseases [191]. Recent studies have shown that the VP1 region of PVB19 has a phospholipase A2 (PLA2)-like activity that can produce lysophosphatidylcholine and lysophosphatidic acid [192,193]. Lysophosphatidylcholine can cause adverse effects on endothelial cells such as enhanced inflammation, disruption of mitochondrial integrity, induction of apoptosis and altered ion channel regulation [194].…”

Section: Pvb19mentioning

confidence: 99%

Virus-Host Interactions of Enteroviruses and Parvovirus B19 in Myocarditis

Peischard

Strutz‐Seebohm

et al. 2021

Cell Physiol Biochem

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Viral diseases are a major threat to modern society and the global health system. It is therefore of utter relevance to understand the way viruses affect the host as a basis to find new treatment solutions. The understanding of viral myocarditis (VMC) is incomplete and effective treatment options are lacking. This review will discuss the mechanism, effects, and treatment options of the most frequent myocarditis-causing viruses namely enteroviruses such as Coxsackievirus B3 (CVB3) and Parvovirus B19 (PVB19) on the human heart. Thereby, we focus on: 1. Viral entry: CVB3 use Coxsackievirus-Adenovirus-Receptor (CAR) and Decay Accelerating Factor (DAF) to enter cardiac myocytes while PVB19 use the receptor globoside (Gb4) to enter cardiac endothelial cells. 2. Immune system responses: The innate immune system mediated by activated cardiac toll-like receptors (TLRs) worsen inflammation in CVB3-infected mouse hearts. Different types of cells of the adaptive immune system are recruited to the site of inflammation that have either protective or adverse effects during VMC. 3. Autophagy: CVB3 evades autophagosomal degradation and misuses the autophasomal pathway for viral replication and release. 4. Viral replication sites: CVB3 promotes the formation of double membrane vesicles (DMVs), which it uses as replication sites. PVB19 uses the host cell nucleus as the replication site and uses the host cell DNA replication system. 5. Cell cycle manipulation: CVB3 attenuates the cell cycle at the G1/S phase, which promotes viral transcription and replication. PVB19 exerts cell cycle arrest in the S phase using its viral endonuclease activity. 6. Regulation of apoptosis: Enteroviruses prevent apoptosis during early stages of infection and promote cell death during later stages by using the viral proteases 2A and 3C, and viroporin 2B. PVB19 promotes apoptosis using the non-structural proteins NS1 and the 11 kDa protein. 7. Energy metabolism: Dysregulation of respiratory chain complex expression, activity and ROS production may be altered in CVB3- and PVB19-mediated myocarditis. 8. Ion channel modulation: CVB3-expression was indicated to alter calcium and potassium currents in Xenopus laevis oocytes and rodent cardiomyocytes. The phospholipase 2-like activity of PVB19 may alter several calcium, potassium and sodium channels. By understanding the general pathophysiological mechanisms of well-studied myocarditis-linked viruses, we might be provided with a guideline to handle other less-studied human viruses.

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Role of lysophosphatidic acid in ion channel function and disease

Cited by 22 publications

References 114 publications

An Updated Review of Lysophosphatidylcholine Metabolism in Human Diseases

An Updated Review of Lysophosphatidylcholine Metabolism in Human Diseases

TRP ion channels: Proteins with conformational flexibility

Virus-Host Interactions of Enteroviruses and Parvovirus B19 in Myocarditis

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