Dataset Information

Stress responses in human cells

ABSTRACT: Proteomes of cytoplasmic particles from HEK293T cells after oxidative shock (sodium arsenite)

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Suspension Culture

SUBMITTER: Natalia Demeshkina

LAB HEAD: Adrian R. Ferré-D'Amaré

PROVIDER: PXD053091 | Pride | 2025-08-25

REPOSITORIES: Pride

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Publications

Large-scale purifications reveal yeast and human stress granule cores are heterogeneous particles with complex transcriptomes and proteomes.

Demeshkina Natalia A NA Ferré-D'Amaré Adrian R AR

Cell reports 20250523 6

Stress granules are a conserved response of eukaryotic cells to environmental insults. These cytoplasmic ribonucleoprotein condensates have hitherto been primarily studied by microscopy, which showed previously that they comprise dense ∼200 nm cores embedded in a diffuse shell. We have developed large-scale purifications of budding yeast and mammalian (HEK293T cell) stress granule cores that do not rely on immunoprecipitation of candidate protein constituents. These unbiased preparations reveal ...[more]

PMID: 40413746

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Project description:Arsenic (As) exposure is a significant worldwide environmental health concern. Low dose, chronic arsenic exposure has been associated with higher risk of skin, lung, and bladder cancer, as well as cardiovascular disease and diabetes. While arsenic-induced biological changes play a role in disease pathology, little is known about the dynamic cellular changes due to arsenic exposure and withdrawal. In these studies, we seek to understand the molecular mechanisms behind the biological changes induced by chronic low doses of arsenic exposure. We used a comprehensive approach involving chromatin structural studies and mRNA microarray analyses to determine how chromatin structure and gene expression patterns change in response to chronic low dose arsenic exposure and its subsequent withdrawal. Our results show that cells exposed to low doses of sodium arsenite have distinct temporal and coordinated chromatin, gene expression and miRNA changes that are consistent with differentiation and activation of multiple biochemical pathways. Most of these temporal patterns in gene expression are reversed when arsenic was withdrawn. However, some of the gene expression patterns remained altered, plausibly as a result of an adaptive response by these cells. Additionally, these gene expression patterns correlated with changes in chromatin structure, further solidifying the role of chromatin structure in gene regulatory changes due to arsenite exposure. Lastly, we show that arsenite exposure influences gene regulation both at the transcription initiation as well as at the splicing level. Thus our results suggest that general patterns of alternative splicing, as well as expression of particular gene regulators, can be indicative of arsenite-induced cell transformation. A total of eight (8) samples with two biological replicates under four separate conditions: wild-type treated with deionized H2O for 36 days (NT); chronic low-dose arsenic exposure of 1 uM of sodium arsenite (iAs-T) for 36 days; chronic arsenic exposure of 1 uM of sodium arsenite for 26 days followed by removal of sodium arsenite for 10 days, measured at day 36 (iAs-Rev); and chronic arsenic exposure of 1 uM of sodium arsenite for 26 days, followed by removal of sodium arsenite exposure for 10 days, followed by 1 uM of chronic sodium arsenite exposure for 10 days (measured at day 46) (iAs-Rev-T).

			Action	DRS
	mSGCs_1.msf	Msf
	mSGCs_1.raw	Raw
	mSGCs_2.msf	Msf
	mSGCs_2.raw	Raw
	mSGCs_3.msf	Msf