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Inhibition of AK4 expression increases drug sensitivity and elevates mitochondrial ATP synthesis

ABSTRACT: Adenylate kinase 4 (AK4) is localized in the mitochondrial matrix, and is believed to be involved in stress, drug resistance, the malignant transformation of cancer, and ATP regulation. We produced AK4 knockdown HeLa cells by using shRNA and used these to analyze resistance, and found that sensitivity to hypoxia and drugs increased.

ORGANISM(S): Homo sapiens

PROVIDER: GSE61843 | GEO | 2016/03/31

SECONDARY ACCESSION(S): PRJNA262546

REPOSITORIES: GEO

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Inhibition of AK4 expression increases drug sensitivity and elevates mitochondrial ATP synthesis

Project description:Adenylate kinase 4 (AK4) is localized in the mitochondrial matrix, and is believed to be involved in stress, drug resistance, the malignant transformation of cancer, and ATP regulation. We produced AK4 knockdown HeLa cells by using shRNA and used these to analyze resistance, and found that sensitivity to hypoxia and drugs increased. 3 samples of HeLa cells haboring AK4 shRNA plasmids and 4 samples of HeLa cells haboring control shRNA plasmid.

2016-03-31 | E-GEOD-61843 | biostudies-arrayexpress

Adenylate kinase 4 Promotes the expression of Inflammatory Genes in Macrophages via Hif-1a

Project description:Macrophages comprise the first line of defense against various pathogens. Classically activated macrophages (M1), induced by IFNg and LPS, express a high level of inflammatory cytokines and contribute to inflammatory processes. By contrast, alternatively activated macrophages (M2) are induced by IL-4/IL-13, produce IL-10, and display anti-inflammatory activity. Adenylate kinase 4 (Αk4), an enzyme that transfers phosphate group among ATP/GTP, AMP, and ADP, is a key modulator of ATP and is involved in maintaining the homeostasis of cellular nucleotides which is essential for the function of cells. However, its role in regulating the function of macrophages is not fully understood. Here we report that the expression of Ak4 is induced in M1 but not M2 macrophages. Suppressing the expression of Ak4 in M1 macrophages with shRNA enhances the production of ATP. RNA-seq analysis identifies several inflammation-related genes, including Il1b, Il6, Tnfa, Nos2 and Hif1a, as downstream targets of Ak4. We further demonstrate that Ak4 and Hif1a form a positive feedback loop in sustaining the expression of the inflammation-related genes. Our data depict a potential mechanism linking energy consumption and inflammation in macrophages.

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Integrated Analysis of Genes Encoding ATP-Dependent Chromatin Remodelers Identifies CHD7 as a Potential Target for Colorectal Cancer Therapy

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Impairment of vesicular ATP release affects glucose metabolism and increases insulin sensitivity.

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Expression data from AK4 overexpression in CL1-0 lung cancer cell line and AK4 knockdown in CL1-5 lung cancer cell line

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