Cytotoxic, genotoxic and cell-cycle disruptive effects of thio-dimethylarsinate in cultured human cells and the role of glutathione

Switch/sucrose non-fermentable (SWI/SNF)-related matrix-associated actin-dependent regulator of chromatin (SMARC) subfamily B member 1 (SMARCB1) is a core subunit of the switch/sucrose non-fermentable (SWI/SNF) complex, one of the adenosine triphosphate (ATP)-dependent chromatin remodeler complexes. The unique role of SMARCB1 has been reported in various cellular contexts. Here, we focused on the general role of the ubiquitous expression of SMARCB1 in a normal cell state. We selected ARPE19 (human primary retinal pigment epithelium) and IMR90 (from human fetal lung fibroblasts) cell lines as they have completely different contexts. Furthermore, although these cell lines have been immortalized, they are relatively close to normal human cells. The loss of SMARCB1 in ARPE19 and IMR90 cells reduced cell cycle progression via the upregulation of P21. Transcriptome analysis followed by SMARCB1 knockdown in both cell lines revealed that SMARCB1 was not only involved in cell maintenance but also conferred immunomodulation. Of note, SMARCB1 bound to interleukin (IL) 6 promoter in a steady state and dissociated in an active immune response state, suggesting that SMARCB1 was a direct repressor of IL6, which was further confirmed via loss- and gain-of-function studies. Taken together, we demonstrated that SMARCB1 is a critical gatekeeper molecule of the cell cycle and immune response.

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Cell Cycle Delay, Mitochondrial Stress and Uptake of Hydrophobic Cations Induced by Sunscreens in Cultured Human Cells

Photochemistry and Photobiology ◽

10.1111/j.1751-1097.1999.tb03336.x ◽

1999 ◽

Vol 69 (5) ◽

pp. 611-616 ◽

Cited By ~ 10

Author(s):

Chunxia Xu ◽

Peter G. Parsons

Keyword(s):

Cell Cycle ◽

Human Cells ◽

Mitochondrial Stress ◽

Cell Cycle Delay ◽

Cultured Human Cells

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Induction of chromosome aberrations in cultured human cells by ethylenimine and its relation to cell cycle

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis ◽

10.1016/0027-5107(67)90112-1 ◽

1967 ◽

Vol 4 (1) ◽

pp. 83-89 ◽

Cited By ~ 34

Author(s):

Tsueng-Hsing Chang ◽

Flora T. Elequin

Keyword(s):

Cell Cycle ◽

Chromosome Aberrations ◽

Human Cells ◽

Cultured Human Cells

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Gold Resistance in Cultured Human Cells Possible Role of Metallothionein

Scandinavian Journal of Rheumatology ◽

10.3109/03009748309095342 ◽

1983 ◽

Vol 12 (sup51) ◽

pp. 42-44 ◽

Cited By ~ 3

Author(s):

Anne Glennås

Keyword(s):

Human Cells ◽

Cultured Human Cells

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Characterization of DNA polymerase β mRNA: cell-cycle and growth response in cultured human cells

Nucleic Acids Research ◽

10.1093/nar/16.20.9587 ◽

1988 ◽

Vol 16 (20) ◽

pp. 9587-9596 ◽

Cited By ~ 48

Author(s):

B.Z. Zmudzka ◽

A. Fomace ◽

J. Collins ◽

S.H. Wilson

Keyword(s):

Cell Cycle ◽

Dna Polymerase ◽

Growth Response ◽

Human Cells ◽

Dna Polymerase Β ◽

Cultured Human Cells

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Deletion of the lactoperoxidase gene causes multisystem inflammation and tumors in mice

Scientific Reports ◽

10.1038/s41598-021-91745-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jayden Yamakaze ◽

Zhe Lu

Keyword(s):

Redox Reaction ◽

Human Cells ◽

Mutant Mice ◽

Biological Role ◽

Protective Mechanism ◽

Enzymatic Mechanism ◽

High Incidence ◽

Cultured Human Cells

AbstractStrongly oxidative H2O2 is biologically important, but if uncontrolled, would lead to tissue injuries. Lactoperoxidase (LPO) catalyzes the redox reaction of reducing highly reactive H2O2 to H2O while oxidizing thiocyanate (SCN−) to relatively tissue-innocuous hypothiocyanite (OSCN−). SCN− is the only known natural, effective reducing-substrate of LPO; humans normally derive SCN− solely from food. While its enzymatic mechanism is understood, the actual biological role of the LPO-SCN− system in mammals remains unestablished. Our group previously showed that this system protected cultured human cells from H2O2-caused injuries, a basis for the hypothesis that general deficiency of such an antioxidative mechanism would lead to multisystem inflammation and tumors. To test this hypothesis, we globally deleted the Lpo gene in mice. The mutant mice exhibited inflammation and lesions in the cardiovascular, respiratory, digestive or excretory systems, neuropathology, and tumors, with high incidence. Thus, this understudied LPO-SCN− system is an essential protective mechanism in vivo.

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