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Gene expression profiling of oxidative stress response of C. elegans aging defective AMPK mutants using massively parallel transcriptome sequencing.

Shin H, Lee H, Fejes AP, Baillie DL, Koo HS, Jones SJ - BMC Res Notes (2011)

Bottom Line: Specifically, we compared the transcriptomes of aak-2 and wild type animals under normal conditions and conditions of induced oxidative stress.The analysis presented in this study has enabled us to identify potential genes involved in stress resistance that may be either directly or indirectly under the control of AAK-2.Furthermore, we have extended our current knowledge of general defense responses of C. elegans against oxidative stress supporting the function for AAK-2 in inhibition of biosynthetic processes, especially lipid synthesis, under oxidative stress and transcriptional regulation of genes involved in reproductive processes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Genome Sciences Centre, BC Cancer Agency, Suite 100 570 West 7th Avenue, Vancouver, British Columbia, Canada V5Z 4S6. sjones@bcgsc.ca.

ABSTRACT

Background: A strong association between stress resistance and longevity in multicellular organisms has been established as many mutations that extend lifespan also show increased resistance to stress. AAK-2, the C. elegans homolog of an alpha subunit of AMP-activated protein kinase (AMPK) is an intracellular fuel sensor that regulates cellular energy homeostasis and functions in stress resistance and lifespan extension.

Findings: Here, we investigated global transcriptional responses of aak-2 mutants to oxidative stress and in turn identified potential downstream targets of AAK-2 involved in stress resistance in C. elegans. We employed massively parallel Illumina sequencing technology and performed comprehensive comparative transcriptome analysis. Specifically, we compared the transcriptomes of aak-2 and wild type animals under normal conditions and conditions of induced oxidative stress. This research has presented a snapshot of genome-wide transcriptional activities that take place in C. elegans in response to oxidative stress both in the presence and absence of AAK-2.

Conclusions: The analysis presented in this study has enabled us to identify potential genes involved in stress resistance that may be either directly or indirectly under the control of AAK-2. Furthermore, we have extended our current knowledge of general defense responses of C. elegans against oxidative stress supporting the function for AAK-2 in inhibition of biosynthetic processes, especially lipid synthesis, under oxidative stress and transcriptional regulation of genes involved in reproductive processes.

No MeSH data available.


Related in: MedlinePlus

Number of commonly or statistically differentially regulated genes in wild type and aak-2 mutants in response to oxidative stress and examples. (A) Venn diagram showing numbers of commonly up or (B) down-regulated genes with statistically significant gene expression level changes in wild type and aak-2 mutants in response to oxidative stress relative to wild type (overlapping regions) as well as numbers of genes up or down-regulated exclusively in stressed wild type or stressed aak-2 mutants relative to wild type (non-overlapping regions). Numbers in brackets indicate genes that showed the most difference in gene expression relative to wild type between the two libraries, stressed wild type and stressed aak-2 (i.e. genes that showed significant changes in one library (i.e. Log2 ratio relative to wild type greater or less than /0.7/, p-val < 0.01), but showed negligible changes (i.e. Log2 ratio relative to wild type greater or less than ~/0.3/) or significantly changed in the opposite direction in the other library). For instance, there is a relatively large subset of genes in brackets (125) significantly up-regulated in aak-2 mutants in response to oxidative stress but either insignificantly regulated or significantly down-regulated in wild type under oxidative stress. (C) UCSC browser view of hsp-16.2 and hsp-16.41 with the sequence reads aligned to the gene models. Four samples (Stressed wild type (N2), Stressed aak-2, Unstressed wild type (N2), Unstressed aak-2) are shown. It is evident hsp-16.2 and hsp-16.41 are much more highly expressed in stressed wild type and stressed aak-2 mutants compared to unstressed wild type and unstressed aak-2 mutants, especially in stressed aak-2 mutants. Note: The scales for the minimum and maximum number of reads for the four samples are different. (D) UCSC browser view of fat-7 with the sequence reads aligned to the gene model. Four samples (Stressed wild type, Stressed aak-2, Unstressed wild type, Unstressed aak-2) are shown. As indicated by the number of sequence reads mapped, fat-7is much more highly expressed in aak-2 mutants (stressed and unstressed) compared to wild type (stressed and unstressed). Note: The scales for the minimum and maximum number of reads for the four samples are different.
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Figure 3: Number of commonly or statistically differentially regulated genes in wild type and aak-2 mutants in response to oxidative stress and examples. (A) Venn diagram showing numbers of commonly up or (B) down-regulated genes with statistically significant gene expression level changes in wild type and aak-2 mutants in response to oxidative stress relative to wild type (overlapping regions) as well as numbers of genes up or down-regulated exclusively in stressed wild type or stressed aak-2 mutants relative to wild type (non-overlapping regions). Numbers in brackets indicate genes that showed the most difference in gene expression relative to wild type between the two libraries, stressed wild type and stressed aak-2 (i.e. genes that showed significant changes in one library (i.e. Log2 ratio relative to wild type greater or less than /0.7/, p-val < 0.01), but showed negligible changes (i.e. Log2 ratio relative to wild type greater or less than ~/0.3/) or significantly changed in the opposite direction in the other library). For instance, there is a relatively large subset of genes in brackets (125) significantly up-regulated in aak-2 mutants in response to oxidative stress but either insignificantly regulated or significantly down-regulated in wild type under oxidative stress. (C) UCSC browser view of hsp-16.2 and hsp-16.41 with the sequence reads aligned to the gene models. Four samples (Stressed wild type (N2), Stressed aak-2, Unstressed wild type (N2), Unstressed aak-2) are shown. It is evident hsp-16.2 and hsp-16.41 are much more highly expressed in stressed wild type and stressed aak-2 mutants compared to unstressed wild type and unstressed aak-2 mutants, especially in stressed aak-2 mutants. Note: The scales for the minimum and maximum number of reads for the four samples are different. (D) UCSC browser view of fat-7 with the sequence reads aligned to the gene model. Four samples (Stressed wild type, Stressed aak-2, Unstressed wild type, Unstressed aak-2) are shown. As indicated by the number of sequence reads mapped, fat-7is much more highly expressed in aak-2 mutants (stressed and unstressed) compared to wild type (stressed and unstressed). Note: The scales for the minimum and maximum number of reads for the four samples are different.

Mentions: The correlation between expression level changes of all genes in response to oxidative stress in wild type and aak-2 mutants is shown in Figure 2A (R2 = 0.58). Figure 2B shows genes commonly up or down-regulated in both wild type and aak-2 mutants in response to oxidative stress relative to wild type (as indicated in green). This correlation is very high as indicated by the linear regression (R2 = 0.92). 239 up-regulated genes and 142 down-regulated genes were common to both wild type and aak-2 mutants (Figure 3A, B), and mostly, the degree of expression level changes of these genes in response to oxidative stress were directly comparable between wild type and aak-2 mutants.


Gene expression profiling of oxidative stress response of C. elegans aging defective AMPK mutants using massively parallel transcriptome sequencing.

Shin H, Lee H, Fejes AP, Baillie DL, Koo HS, Jones SJ - BMC Res Notes (2011)

Number of commonly or statistically differentially regulated genes in wild type and aak-2 mutants in response to oxidative stress and examples. (A) Venn diagram showing numbers of commonly up or (B) down-regulated genes with statistically significant gene expression level changes in wild type and aak-2 mutants in response to oxidative stress relative to wild type (overlapping regions) as well as numbers of genes up or down-regulated exclusively in stressed wild type or stressed aak-2 mutants relative to wild type (non-overlapping regions). Numbers in brackets indicate genes that showed the most difference in gene expression relative to wild type between the two libraries, stressed wild type and stressed aak-2 (i.e. genes that showed significant changes in one library (i.e. Log2 ratio relative to wild type greater or less than /0.7/, p-val < 0.01), but showed negligible changes (i.e. Log2 ratio relative to wild type greater or less than ~/0.3/) or significantly changed in the opposite direction in the other library). For instance, there is a relatively large subset of genes in brackets (125) significantly up-regulated in aak-2 mutants in response to oxidative stress but either insignificantly regulated or significantly down-regulated in wild type under oxidative stress. (C) UCSC browser view of hsp-16.2 and hsp-16.41 with the sequence reads aligned to the gene models. Four samples (Stressed wild type (N2), Stressed aak-2, Unstressed wild type (N2), Unstressed aak-2) are shown. It is evident hsp-16.2 and hsp-16.41 are much more highly expressed in stressed wild type and stressed aak-2 mutants compared to unstressed wild type and unstressed aak-2 mutants, especially in stressed aak-2 mutants. Note: The scales for the minimum and maximum number of reads for the four samples are different. (D) UCSC browser view of fat-7 with the sequence reads aligned to the gene model. Four samples (Stressed wild type, Stressed aak-2, Unstressed wild type, Unstressed aak-2) are shown. As indicated by the number of sequence reads mapped, fat-7is much more highly expressed in aak-2 mutants (stressed and unstressed) compared to wild type (stressed and unstressed). Note: The scales for the minimum and maximum number of reads for the four samples are different.
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Related In: Results  -  Collection

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Figure 3: Number of commonly or statistically differentially regulated genes in wild type and aak-2 mutants in response to oxidative stress and examples. (A) Venn diagram showing numbers of commonly up or (B) down-regulated genes with statistically significant gene expression level changes in wild type and aak-2 mutants in response to oxidative stress relative to wild type (overlapping regions) as well as numbers of genes up or down-regulated exclusively in stressed wild type or stressed aak-2 mutants relative to wild type (non-overlapping regions). Numbers in brackets indicate genes that showed the most difference in gene expression relative to wild type between the two libraries, stressed wild type and stressed aak-2 (i.e. genes that showed significant changes in one library (i.e. Log2 ratio relative to wild type greater or less than /0.7/, p-val < 0.01), but showed negligible changes (i.e. Log2 ratio relative to wild type greater or less than ~/0.3/) or significantly changed in the opposite direction in the other library). For instance, there is a relatively large subset of genes in brackets (125) significantly up-regulated in aak-2 mutants in response to oxidative stress but either insignificantly regulated or significantly down-regulated in wild type under oxidative stress. (C) UCSC browser view of hsp-16.2 and hsp-16.41 with the sequence reads aligned to the gene models. Four samples (Stressed wild type (N2), Stressed aak-2, Unstressed wild type (N2), Unstressed aak-2) are shown. It is evident hsp-16.2 and hsp-16.41 are much more highly expressed in stressed wild type and stressed aak-2 mutants compared to unstressed wild type and unstressed aak-2 mutants, especially in stressed aak-2 mutants. Note: The scales for the minimum and maximum number of reads for the four samples are different. (D) UCSC browser view of fat-7 with the sequence reads aligned to the gene model. Four samples (Stressed wild type, Stressed aak-2, Unstressed wild type, Unstressed aak-2) are shown. As indicated by the number of sequence reads mapped, fat-7is much more highly expressed in aak-2 mutants (stressed and unstressed) compared to wild type (stressed and unstressed). Note: The scales for the minimum and maximum number of reads for the four samples are different.
Mentions: The correlation between expression level changes of all genes in response to oxidative stress in wild type and aak-2 mutants is shown in Figure 2A (R2 = 0.58). Figure 2B shows genes commonly up or down-regulated in both wild type and aak-2 mutants in response to oxidative stress relative to wild type (as indicated in green). This correlation is very high as indicated by the linear regression (R2 = 0.92). 239 up-regulated genes and 142 down-regulated genes were common to both wild type and aak-2 mutants (Figure 3A, B), and mostly, the degree of expression level changes of these genes in response to oxidative stress were directly comparable between wild type and aak-2 mutants.

Bottom Line: Specifically, we compared the transcriptomes of aak-2 and wild type animals under normal conditions and conditions of induced oxidative stress.The analysis presented in this study has enabled us to identify potential genes involved in stress resistance that may be either directly or indirectly under the control of AAK-2.Furthermore, we have extended our current knowledge of general defense responses of C. elegans against oxidative stress supporting the function for AAK-2 in inhibition of biosynthetic processes, especially lipid synthesis, under oxidative stress and transcriptional regulation of genes involved in reproductive processes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Genome Sciences Centre, BC Cancer Agency, Suite 100 570 West 7th Avenue, Vancouver, British Columbia, Canada V5Z 4S6. sjones@bcgsc.ca.

ABSTRACT

Background: A strong association between stress resistance and longevity in multicellular organisms has been established as many mutations that extend lifespan also show increased resistance to stress. AAK-2, the C. elegans homolog of an alpha subunit of AMP-activated protein kinase (AMPK) is an intracellular fuel sensor that regulates cellular energy homeostasis and functions in stress resistance and lifespan extension.

Findings: Here, we investigated global transcriptional responses of aak-2 mutants to oxidative stress and in turn identified potential downstream targets of AAK-2 involved in stress resistance in C. elegans. We employed massively parallel Illumina sequencing technology and performed comprehensive comparative transcriptome analysis. Specifically, we compared the transcriptomes of aak-2 and wild type animals under normal conditions and conditions of induced oxidative stress. This research has presented a snapshot of genome-wide transcriptional activities that take place in C. elegans in response to oxidative stress both in the presence and absence of AAK-2.

Conclusions: The analysis presented in this study has enabled us to identify potential genes involved in stress resistance that may be either directly or indirectly under the control of AAK-2. Furthermore, we have extended our current knowledge of general defense responses of C. elegans against oxidative stress supporting the function for AAK-2 in inhibition of biosynthetic processes, especially lipid synthesis, under oxidative stress and transcriptional regulation of genes involved in reproductive processes.

No MeSH data available.


Related in: MedlinePlus