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TRPM7 regulates quiescent/proliferative metabolic transitions in lymphocytes.

ABSTRACT: A unique property of lymphocytes among all body tissues is their capacity for rapid proliferation in the context of responding to infectious challenges. Lymphocyte proliferation involves a transition from a quiescent metabolic state adjusted to maintain cellular energy homeostasis, to a proliferative metabolic state in which aerobic glycolysis is used to generate energy and biosynthetic precursors necessary for the accumulation of cell mass. Here we show that modulation of TRPM7 channel function in tumor B-lymphocytes directly induces quiescent/proliferative metabolic transitions. As TRPM7 is widely expressed outside of the immune system, our results suggest that TRPM7 may play an active role in regulating metabolic transitions associated with rapid cellular proliferation and malignancy.

SUBMITTER: Sahni J

PROVIDER: S-EPMC3047620 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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TRPM7 regulates quiescent/proliferative metabolic transitions in lymphocytes.

Sahni Jaya J Tamura Richard R Sweet Ian R IR Scharenberg Andrew M AM

Cell cycle (Georgetown, Tex.) 20100925 17

A unique property of lymphocytes among all body tissues is their capacity for rapid proliferation in the context of responding to infectious challenges. Lymphocyte proliferation involves a transition from a quiescent metabolic state adjusted to maintain cellular energy homeostasis, to a proliferative metabolic state in which aerobic glycolysis is used to generate energy and biosynthetic precursors necessary for the accumulation of cell mass. Here we show that modulation of TRPM7 channel function ...[more]

PMID: 20724843

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Project description:Quiescent cells are considered to be dormant. However, recent studies suggest that quiescent fibroblasts possess active metabolic profile and certain functional characteristics. We previously observed that serum-starved quiescent fibroblasts respond to proinflammatory stimuli by robust expression of cyclooxygenase-2 (COX-2), which declines after the quiescent fibroblasts are driven to proliferation. In this study, we elucidated the underlying signaling and transcriptional mechanism and identified by microarray genes with similar differential expression. By using pharmacological inhibitors coupled with gene silencing, we uncovered the key role of protein kinase C ? (PKC?) and extracellular signal regulated protein kinase 1/2 (ERK1/2) signaling in mediating COX-2 expression in quiescent cells. Surprisingly, COX-2 expression in proliferative cells was not blocked by PKC? or ERK1/2 inhibitors due to intrinsic inhibition of PKC? and ERK1/2 in proliferative cells. Restrained COX-2 transcription in proliferative cells was attributable to reduced NF-?B binding. Microarray analysis identified 35 genes whose expressions were more robust in quiescent than in proliferative cells. A majority of those genes belong to proinflammatory cytokines, chemokines, adhesive molecules and metalloproteinases, which require NF-?B for transcription. Quiescent fibroblasts had a higher migratory activity than proliferative fibroblasts as determined by the transwell assay. Selective COX-2 inhibition reduced migration which was restored by prostaglandin E(2). As COX-2 and inflammatory mediators induce DNA oxidation, we measured 8-hydroxydeoxyguanosine (8-OHdG) in quiescent vs. proliferative fibroblasts. PMA-induced 8-OHdG accumulation was significantly higher in quiescent than in proliferative fibroblasts. These findings indicate that quiescent fibroblasts (and probably other quiescent cells) are at the forefront in mounting inflammatory responses through expression of an array of proinflammatory genes via the PKC?/ERK1/2 signaling pathway.

Dataset Information

TRPM7 regulates quiescent/proliferative metabolic transitions in lymphocytes.

Publications

TRPM7 regulates quiescent/proliferative metabolic transitions in lymphocytes.

Similar Datasets

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