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Gupta, P and Singh, P and Pandey, HS and Seth, P and Mukhopadhyay, CK (2019) Phosphoinositide-3-Kinase Inhibition Elevates Ferritin Level Resulting Depletion of Labile Iron Pool and Blocking of Glioma Cell Proliferation. Biochim Biophys Acta Gen Subj., 1863 (3). pp. 547-564.

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Abstract

BACKGROUND: Elevated endogenous phosphoinositide-3-kinase (PI3K) activity is critical for cell proliferation in gliomas. Iron availability is one of the essential factors for cell growth and proliferation. However, any relation between PI3K and cellular iron homeostasis has not been understood so far. METHODS: Glioma cells and human primary astrocytes were treated with class I PI3K inhibitors to examine regulation of iron homeostasis components. Regulation of ferritin was detected at mRNA and translational level. Labile iron pool (LIP) and cell proliferation were examined in glioma cells and human primary astrocytes. RESULTS: Blocking of PI3K activity elevated ferritin level by 6-10 folds in glioma cells by augmenting mRNA expression of ferritin subunits and also by influencing ferritin translation. IRE-IRP interaction was affected due to conversion of IRP1 to cytosolic aconitase that was influenced by increased iron-sulfur scaffold protein iron-sulfur cluster assembly enzyme (ISCU) level. Elevated ferritin sequestered LIP to affect cell proliferation that was reversed in silencing ferritin by siRNAs of ferritin-H and ISCU. Human primary astrocyte with little PI3K activity did not show any change in ferritin level, LIP and cell proliferation by PI3K inhibitors.

Item Type: Article
Subjects: Neurodegenerative Disorders
Neuro-Oncological Disorders
Neurocognitive Processes
Neuronal Development and Regeneration
Informatics and Imaging
Genetics and Molecular Biology
Depositing User: Dr. D.D. Lal
Date Deposited: 17 Jun 2019 09:11
Last Modified: 17 Jun 2019 09:11
URI: http://nbrc.sciencecentral.in/id/eprint/499

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