Dataset Information

The pan-Sirtuin inhibitor MC2494 regulates mitochondrial function in a leukemia cell line

ABSTRACT: The involvement of sirtuins (SIRTs) in modulating metabolic and stress response pathways is attracting growing scientific interest. Some SIRT family members are located in mitochondria, dynamic organelles that perform several crucial functions essential for eukaryotic life. Mitochondrial dysfunction has emerged as having a key role in a number of human diseases, including cancer. Here, we investigated mitochondrial damage resulting from treatment with a recently characterized pan-SIRT inhibitor, MC2494. MC2494 was able to block mitochondrial biogenesis and function in terms of ATP synthesis and energy metabolism, suggesting that it might orchestrate cell response to metabolic stress and thereby interfere with tumorigenesis. Targeting mitochondrial function could thus be considered a potential anticancer strategy for use in clinical therapy.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Monocyte, Cell Culture

DISEASE(S): Acute Leukemia,Lymphoma

SUBMITTER: Angela Chambery

LAB HEAD: Angela Chambery

PROVIDER: PXD017508 | Pride | 2021-09-08

REPOSITORIES: Pride

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The Pan-Sirtuin Inhibitor MC2494 Regulates Mitochondrial Function in a Leukemia Cell Line.

Carafa Vincenzo V Russo Rosita R Della Torre Laura L Cuomo Francesca F Dell'Aversana Carmela C Sarno Federica F Sgueglia Giulia G Di Donato Marzia M Rotili Dante D Mai Antonello A Nebbioso Angela A Cobellis Gilda G Chambery Angela A Altucci Lucia L

Frontiers in oncology 20200521

The involvement of sirtuins (SIRTs) in modulating metabolic and stress response pathways is attracting growing scientific interest. Some SIRT family members are located in mitochondria, dynamic organelles that perform several crucial functions essential for eukaryotic life. Mitochondrial dysfunction has emerged as having a key role in a number of human diseases, including cancer. Here, we investigated mitochondrial damage resulting from treatment with a recently characterized pan-SIRT inhibitor, ...[more]

PMID: 32528892

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Project description:Human histomonocytic U937 cells exhibit macrophage-like properties after phorbol ester stimulation. Accumulating evidence demonstrated that remarkable number of transcripts changed in their amount at total RNA levels. However, post-transcriptional regulation has not been fully elucidated in this model. Thus, we compared expression profiles between polysomal and cytoplasmic RNAs before and after phorbol 12-myristate 13-acetate stimulation (48h, 32nM). Table 1: Detailed description of the expression data of human histomonocytic cell line U937 cells. Data of total cytoplasmic and polysomal fractions before and after PMA stimulation is shown. This table contains all spot data except: 1) saturated spots, 2) undetectable spots, 3) stained spots, and 4) spots only detected in less than one samples. Column A: Gene symbol (âI_xxxxxxâ is corresponding to EST clones); Column B: Genbank accession no. Column C: Description; Column D: Average value of expression levels in total cytoplasmic fraction in the absence of PMA; Column E: Average value of expression levels in total cytoplasmic fraction in the presence of PMA (32nM, 48h); Column F: Average value of expression levels in polysomal fraction in the absence of PMA; Column G: Average value of expression levels in polysomal fraction in the presence of PMA; Column H: Expression ratio of polysome, PMA (-) to cytoplasm, PMA(-); Column I: Expression ratio of polysome, PMA (+) to cytoplasm, PMA(+); Column J: Expression ratio of cytoplasm, PMA (+) to cytoplasm, PMA(-); Column K: Expression ratio of polysome, PMA (+) to polysome, PMA(-); Column L: Different expression between polysome, PMA (-) and cytoplasm, PMA(-): different=1; Column M: Different expression between polysome, PMA (+) and cytoplasm, PMA(+): different=1; Column N: Different expression between cytoplasm, PMA (+) and cytoplasm, PMA(-): different=1; Column O: Different expression between polysome, PMA (+) and polysome, PMA(-): different=1; ; Table 2: Candidates post-transcriptionally regulated by PMA. We extracted 105 transcripts whose expression levels were altered only in either fraction accompanied by changes in polysome/cytoplasm expression ratio. Column A: Gene symbol (âI_xxxxxxâ is corresponding to EST clones); Column B: Genbank accession no. Column C: Description; Column D: Average value of expression levels in total cytoplasmic fraction in the absence of PMA; Column E Average value of expression levels in total cytoplasmic fraction in the presence of PMA; Column F: Average value of expression levels in polysomal fraction in the absence of PMA; Column G: Average value of expression levels in polysomal fraction in the presence of PMA; Column H: Expression ratio of polysome, PMA (-) to cytoplasm, PMA(-); Column I: Expression ratio of polysome, PMA (+) to cytoplasm, PMA(+); Column J: Expression ratio of cytoplasm, PMA (+) to cytoplasm, PMA(-); Column K: Expression ratio of polysome, PMA (+) to polysome, PMA(-)

			Action	DRS
	TMT_U937_search.msf	Msf
	U937_TMT_1.raw	Raw
	U937_TMT_2.raw	Raw
	U937_TMT_3.raw	Raw