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| Status |
Public on May 01, 2019 |
| Title |
The LKB1/AMPK pathway is a central mediator of the hepatic xenobiotic response |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The serine/threonine kinase LKB1 is a tumor suppressor gene which also plays key roles in metabolic function in peripheral tissues through its direct phosphorylation and activation of the AMP-activated protein kinase (AMPK). The LKB1/AMPK pathway plays key roles in the liver in suppressing transcriptional programs of gluconeogenesis and lipogenesis, and hepatic LKB1 is required for the ability of the type 2 diabetes agent metformin to lower blood glucose levels in mice. To more broadly define how the LKB1/AMPK pathway controls hepatic metabolism, transcriptional profiling was employed using mice with an inducible liver-specific deletion of Lkb1. Unexpectedly, LKB1/AMPK signaling broadly controls the expression of many phase I xenobiotic metabolism genes, including several members of the cytochrome P450 family. In particular, expression of CYP2E1, an important mediator of drug detoxification, was markedly reduced upon LKB1 loss. LKB1 liver-specific knockout mice exposed to hepatocarcinogens, exhibited marked resistance to carcinogen-induced hepatocyte apoptosis, proliferation, senescence, and liver fibrosis and tumorigenesis.
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| Overall design |
Total RNA obtained from livers of wild-type and LKB liver-specific knockout mice treated with CCL4, AICAR, or control mineral oil or saline.
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| Contributor(s) |
Kohnz RA, Shaw RJ, Yu RT |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
May 25, 2010 |
| Last update date |
May 01, 2019 |
| Contact name |
Ruth T Yu |
| E-mail(s) |
[email protected]
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| Phone |
858-453-4100
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| Organization name |
Salk Institute
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| Street address |
10010 N. Torrey Pines Rd.
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| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
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| Platforms (1) |
| GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
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| Samples (16)
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| GSM546670 |
wild-type mice treated with mineral oil_A |
| GSM546671 |
wild-type mice treated with mineral oil_B |
| GSM546672 |
LKB liver-specific knockout mice treated with mineral oil_A |
| GSM546673 |
LKB liver-specific knockout mice treated with mineral oil_B |
| GSM546674 |
wild-type mice treated with CCL4_A |
| GSM546675 |
wild-type mice treated with CCL4_B |
| GSM546676 |
LKB liver-specific knockout mice treated with CCL4_A |
| GSM546677 |
LKB liver-specific knockout mice treated with CCL4_B |
| GSM546678 |
wild-type mice treated with saline_A |
| GSM546679 |
wild-type mice treated with saline_B |
| GSM546680 |
LKB liver-specific knockout mice treated with saline_A |
| GSM546681 |
LKB liver-specific knockout mice treated with saline_B |
| GSM546682 |
wild-type mice treated with AICAR_A |
| GSM546683 |
wild-type mice treated with AICAR_B |
| GSM546684 |
LKB liver-specific knockout mice treated with AICAR_A |
| GSM546685 |
LKB liver-specific knockout mice treated with AICAR_B |
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| Relations |
| BioProject |
PRJNA127197 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE21984_RAW.tar |
3.1 Mb |
(http)(custom) |
TAR |
| GSE21984_non-normalized_data.txt.gz |
2.5 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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