Molecular biomarkers of phospholipidosis in rat blood and heart after amiodarone treatment

Bocchini, Nicola; Giantin, Mery; Crivellente, Federica; Ferraresso, Serena; Faustinelli, Ivo; Dacasto, Mauro; Cristofori, Patrizia

doi:10.1002/jat.2992

Cited by 8 publications

(4 citation statements)

References 65 publications

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“…In addition, in liver tissue from Hexb / mice and DIPL rats, a striking remodeling of the Cer content was detected. Although an alteration of sphingolipid metabolism has been hypothesized (59), it is the first time, to our knowledge, that Cer concentrations have been shown to be affected in DIPL. Changes in Cer concentrations have been linked to many diseases, including neurodegenerative diseases such as Alzheimer's disease (60)(61)(62)(63).…”

Section: Discussionmentioning

confidence: 87%

Alterations in endo-lysosomal function induce similar hepatic lipid profiles in rodent models of drug-induced phospholipidosis and Sandhoff disease

Lecommandeur

Baker

Cox

et al. 2017

Journal of Lipid Research

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Drug-induced phospholipidosis (DIPL) is characterized by an increase in the phospholipid content of the cell and the accumulation of drugs and lipids inside the lysosomes of affected tissues, including in the liver. Although of uncertain pathological significance for patients, the condition remains a major impediment for the clinical development of new drugs. Human Sandhoff disease (SD) is caused by inherited defects of the β subunit of lysosomal β-hexosaminidases (Hex) A and B, leading to a large array of symptoms, including neurodegeneration and ultimately death by the age of 4 in its most common form. The substrates of Hex A and B, gangliosides GM2 and GA2, accumulate inside the lysosomes of the CNS and in peripheral organs. Given that both DIPL and SD are associated with lysosomes and lipid metabolism in general, we measured the hepatic lipid profiles in rodent models of these two conditions using untargeted LC/MS to examine potential commonalities. Both model systems shared a number of perturbed lipid pathways, notably those involving metabolism of cholesteryl esters, lysophosphatidylcholines, bis(monoacylglycero)phosphates, and ceramides. We report here profound alterations in lipid metabolism in the SD liver. In addition, DIPL induced a wide range of lipid changes not previously observed in the liver, highlighting similarities with those detected in the model of SD and raising concerns that these lipid changes may be associated with underlying pathology associated with lysosomal storage disorders.

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Section: Discussionmentioning

confidence: 87%

Alterations in endo-lysosomal function induce similar hepatic lipid profiles in rodent models of drug-induced phospholipidosis and Sandhoff disease

Lecommandeur

Baker

Cox

et al. 2017

Journal of Lipid Research

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“…However, arachidonic acid may be lowered as result of down‐regulation of Pla2g2e (log2 fold change = −1.74). It was reported that the occurrence of cardiovascular disease is closely related to Pla2g2a .…”

Section: Resultsmentioning

confidence: 99%

Identification and analysis of a key long non‐coding RNAs (lncRNAs)‐associated module reveal functional lncRNAs in cardiac hypertrophy

Zhang

Feng

Song

et al. 2017

J Cellular Molecular Medi

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Cardiac hypertrophy (CH) is a common disease that originates from long-term heart pressure overload and finally leads to heart failure. Recently, long non-coding RNAs (lncRNAs) have attracted attention because they have broad and crucial functions in regulating complex biological processes. Some studies had found that lncRNAs play vital roles in complex cardiovascular diseases. However, the function and mechanism of lncRNAs in CH have not been elucidated. In our study, to investigate the potential roles of lncRNAs in CH, the Cardiac Hypertrophy-associated LncRNAs-Protein coding genes Network (CHLPN) was constructed by integrating gene microarray re-annotation and subpathway enrichment analyses. After performing random walking with restart in CHLPN, we predicted 21 significant risk lncRNAs, of which 7 (Kis2, 1700110K17Rik, Gm17501, E330017L17Rik, C630043F03Rik, Gm9866 and Ube4bos1) formed a close module with their co-expressed protein-coding genes (PCGs). We found that the module might play crucial roles in the development of CH. In particular, 44 PCGs that were co-expressed with six lncRNAs were enriched in CH-related biological processes and pathways. We also found that some lncRNAs participated in the competitive endogenous RNA cross-talk that might be involved in CH. These results indicate that the functional lncRNAs are related to post-transcriptional regulation and could shed light on a new molecular diagnostic target of CH.

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“…BMP increase in cells and tissues was reported in various disorders such as cationic amphiphilic drugs (CAD)-induced phospholipidosis and genetic lysosomal storage diseases (LSDs) associated with endolysosomal dysfunction characterized by accumulation of undigested material and secondary metabolites [27][28][29][30][31]. The CAD toxicity, a major concern in drug development, is linked to this build-up of drug and undigested compounds inside the acidic endolysosomal compartment visualized by the formation of vacuoles and concentric multi-lamellar inclusions [32,33].…”

Section: Introductionmentioning

confidence: 99%

Bis(monoacylglycero)phosphate, a new lipid signature of endosome-derived extracellular vesicles

et al. 2020

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Molecular biomarkers of phospholipidosis in rat blood and heart after amiodarone treatment

Cited by 8 publications

References 65 publications

Alterations in endo-lysosomal function induce similar hepatic lipid profiles in rodent models of drug-induced phospholipidosis and Sandhoff disease

Alterations in endo-lysosomal function induce similar hepatic lipid profiles in rodent models of drug-induced phospholipidosis and Sandhoff disease

Identification and analysis of a key long non‐coding RNAs (lncRNAs)‐associated module reveal functional lncRNAs in cardiac hypertrophy

Bis(monoacylglycero)phosphate, a new lipid signature of endosome-derived extracellular vesicles

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