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Brefeldin A activates CHOP promoter at the AARE, ERSE and AP-1 elements

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Abstract

Brefeldin A induces apoptosis in PC-3 and MCF-7 cells at a concentration of 30 ng/ml. RT-PCR analyses showed up-regulation of CHOP/GADD153 and splicing of XBP-1 mRNA in brefeldin A-treated cells. CHOP promoter-luciferase reporter assays demonstrated activation of AARE, ERSE, and AP-1 elements of CHOP promoter by brefeldin A treatment. The activation of these elements was not affected by preincubation of cells with N-acetyl-cysteine (NAC), l-buthionine-(S,R)-sulfoximine (BSO), and c-Jun N-terminal kinase (JNK) inhibitor (SP600125), suggesting that activation of CHOP promoter by brefeldin A may not involve oxidative stress or JNK signaling pathway. On the other hand, brefeldin A-induced apoptosis was not affected by NAC and BSO pretreatment, but was completely suppressed by JNK inhibitor pretreatment. Our results suggest that although CHOP is up-regulated by brefeldin A, it is not a major mediator of brefeldin A-induced apoptosis.

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Abbreviations

AARE:

Amino acid response element

BFA:

Brefeldin A

BSO:

l-Buthionine-(S,R)-sulfoximine

ER:

Endoplasmic reticulum

ERSE:

ER Stress response element

JNK:

c-Jun N-terminal kinase

NAC:

N-Acetyl-cysteine

PDTC:

Pyrrolidine dithiocarbamate

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Acknowledgments

This project is funded, in part, under a grant with the Pennsylvania Department of Health. The Department specifically disclaims responsibility for any analyses, interpretations, or conclusions.

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  1. Department of Pathology and Laboratory Medicine, Albert Einstein Medical Center, 5501 Old York Road, Korman 214, Philadelphia, PA, 19141-3098, USA

    Simon C. M. Kwok & Ierachmiel Daskal

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Correspondence to Simon C. M. Kwok.

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Kwok, S.C.M., Daskal, I. Brefeldin A activates CHOP promoter at the AARE, ERSE and AP-1 elements. Mol Cell Biochem 319, 203–208 (2008). https://doi.org/10.1007/s11010-008-9893-3

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  • DOI: https://doi.org/10.1007/s11010-008-9893-3

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