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Transcriptomic Analysis Unveils Correlations between Regulative Apoptotic Caspases and Genes of Cholesterol Homeostasis in Human Brain

Authors: Picco, Raffaella; Tomasella, Andrea; FOGOLARI, Federico; BRANCOLINI, Claudio;

Transcriptomic Analysis Unveils Correlations between Regulative Apoptotic Caspases and Genes of Cholesterol Homeostasis in Human Brain

Abstract

Regulative circuits controlling expression of genes involved in the same biological processes are frequently interconnected. These circuits operate to coordinate the expression of multiple genes and also to compensate dysfunctions in specific elements of the network. Caspases are cysteine-proteases with key roles in the execution phase of apoptosis. Silencing of caspase-2 expression in cultured glioblastoma cells allows the up-regulation of a limited number of genes, among which some are related to cholesterol homeostasis. Lysosomal Acid Lipase A (LIPA) was up-regulated in two different cell lines in response to caspase-2 down-regulation and cells silenced for caspase-2 exhibit reduced cholesterol staining in the lipid droplets. We expanded this observation by large-scale analysis of mRNA expression. All caspases were analyzed in terms of co-expression in comparison with 166 genes involved in cholesterol homeostasis. In the brain, hierarchical clustering has revealed that the expression of regulative apoptotic caspases (CASP2, CASP8 CASP9, CASP10) and of the inflammatory CASP1 is linked to several genes involved in cholesterol homeostasis. These correlations resulted in altered GBM (Glioblastoma Multiforme), in particular for CASP1. We have also demonstrated that these correlations are tissue specific being reduced (CASP9 and CASP10) or different (CASP2) in the liver. For some caspases (CASP1, CASP6 and CASP7) these correlations could be related to brain aging.

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Keywords

Science, Apoptosis, Transcriptomics; cholesterol; apoptosis; PROLIFERATOR-ACTIVATED RECEPTORS; DENSITY-LIPOPROTEIN RECEPTORS; CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; CELL-DEATH; ENDOTHELIAL LIPASE; HIPPOCAMPAL-NEURONS; SIGNALING PATHWAYS; CYTOCHROME P450S, Cell Line, Tumor, Homeostasis, Humans, RNA, Messenger, Caspase 10, Oligonucleotide Array Sequence Analysis, Caspase 3, Q, Caspase 1, R, Caspase 2, Brain, Caspase 9, Gene Expression Regulation, Neoplastic, Cysteine Endopeptidases, Cholesterol, Organ Specificity, Medicine, Glioblastoma, Research Article

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
9
Average
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Average
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