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Transcriptomic analysis unveils correlations between regulative apoptotic caspases and genes of cholesterol homeostasis in human brain.

Picco R, Tomasella A, Fogolari F, Brancolini C - PLoS ONE (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical and Biological Sciences, Università degli Studi di Udine, Udine, Italy.

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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Related in: MedlinePlus

Analysis of cholesterol and caspase genes expression with aging in anterior prefrontal cortex.A. Bar plot displaying the age frequencies of the samples used in the analysis. B. Dot plot of ranked correlations of the 129 genes involved in cholesterol homeostasis/steroidogenesis and caspases respect to age. C. Dot plot of ranked correlations of genes involved in cholesterol homeostasis/steroidogenesis and caspases that scored significant expression correlation with respect to age. We applied the Spearman method (Benjamini and Hockberg correction). P<0.05.
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pone-0110610-g008: Analysis of cholesterol and caspase genes expression with aging in anterior prefrontal cortex.A. Bar plot displaying the age frequencies of the samples used in the analysis. B. Dot plot of ranked correlations of the 129 genes involved in cholesterol homeostasis/steroidogenesis and caspases respect to age. C. Dot plot of ranked correlations of genes involved in cholesterol homeostasis/steroidogenesis and caspases that scored significant expression correlation with respect to age. We applied the Spearman method (Benjamini and Hockberg correction). P<0.05.

Mentions: Changes in the expression of cholesterol genes in the brain are linked to several physiological/pathological conditions including, regeneration, plasticity, circadian rhythms, diet, degeneration, social behavior and also the presence of several different cell linages [37], [38], [43], [58], [69], [74], [77], [83], [92]. To understand the significance of the described correlations, we decided to interrogate more precisely the public available datasets used in our studies. We restricted our inquiries to one dataset (GSE 17612) in which, information about the specific brain area (the anterior prefrontal cortex/Brodmann area 10) and subjects age were available. 23 microarray of normal brain met these requirements. Age distribution is shown in figure 8A. Cholesterol and caspase genes were ranked accordingly to the Spearman method, respect to the age of the subjects. Figure 8B illustrates that the expression of a set of cholesterol genes shows a good inverse correlation respect to age (green dots) and on the opposite, the expression of a different set of genes increases with aging (blue dots).


Transcriptomic analysis unveils correlations between regulative apoptotic caspases and genes of cholesterol homeostasis in human brain.

Picco R, Tomasella A, Fogolari F, Brancolini C - PLoS ONE (2014)

Analysis of cholesterol and caspase genes expression with aging in anterior prefrontal cortex.A. Bar plot displaying the age frequencies of the samples used in the analysis. B. Dot plot of ranked correlations of the 129 genes involved in cholesterol homeostasis/steroidogenesis and caspases respect to age. C. Dot plot of ranked correlations of genes involved in cholesterol homeostasis/steroidogenesis and caspases that scored significant expression correlation with respect to age. We applied the Spearman method (Benjamini and Hockberg correction). P<0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4199739&req=5

pone-0110610-g008: Analysis of cholesterol and caspase genes expression with aging in anterior prefrontal cortex.A. Bar plot displaying the age frequencies of the samples used in the analysis. B. Dot plot of ranked correlations of the 129 genes involved in cholesterol homeostasis/steroidogenesis and caspases respect to age. C. Dot plot of ranked correlations of genes involved in cholesterol homeostasis/steroidogenesis and caspases that scored significant expression correlation with respect to age. We applied the Spearman method (Benjamini and Hockberg correction). P<0.05.
Mentions: Changes in the expression of cholesterol genes in the brain are linked to several physiological/pathological conditions including, regeneration, plasticity, circadian rhythms, diet, degeneration, social behavior and also the presence of several different cell linages [37], [38], [43], [58], [69], [74], [77], [83], [92]. To understand the significance of the described correlations, we decided to interrogate more precisely the public available datasets used in our studies. We restricted our inquiries to one dataset (GSE 17612) in which, information about the specific brain area (the anterior prefrontal cortex/Brodmann area 10) and subjects age were available. 23 microarray of normal brain met these requirements. Age distribution is shown in figure 8A. Cholesterol and caspase genes were ranked accordingly to the Spearman method, respect to the age of the subjects. Figure 8B illustrates that the expression of a set of cholesterol genes shows a good inverse correlation respect to age (green dots) and on the opposite, the expression of a different set of genes increases with aging (blue dots).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical and Biological Sciences, Università degli Studi di Udine, Udine, Italy.

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.

Show MeSH
Related in: MedlinePlus