Dataset Information

Chalinulasterol, a chlorinated steroid disulfate from the Caribbean sponge Chalinula molitba. Evaluation of its role as PXR receptor modulator.

ABSTRACT: Chalinulasterol (1) a new chlorinated sterol disulfate was isolated from the Caribbean sponge Chalinula molitba. Its structure was elucidated using mass spectrometry and NMR experiments. The possible role of chalinulasterol as modulator of the PXR nuclear receptor was investigated but, in spite of the close structural relationship with the PXR agonist solomonsterol A (2), it showed no activity. The structural requirements for the PXR nuclear receptor activity were discussed.

SUBMITTER: Teta R

PROVIDER: S-EPMC3397446 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Chalinulasterol, a chlorinated steroid disulfate from the Caribbean sponge Chalinula molitba. Evaluation of its role as PXR receptor modulator.

Teta Roberta R Della Sala Gerardo G Renga Barbara B Mangoni Alfonso A Fiorucci Stefano S Costantino Valeria V

Marine drugs 20120614 6

Chalinulasterol (1) a new chlorinated sterol disulfate was isolated from the Caribbean sponge Chalinula molitba. Its structure was elucidated using mass spectrometry and NMR experiments. The possible role of chalinulasterol as modulator of the PXR nuclear receptor was investigated but, in spite of the close structural relationship with the PXR agonist solomonsterol A (2), it showed no activity. The structural requirements for the PXR nuclear receptor activity were discussed. ...[more]

PMID: 22822379

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Project description:BACKGROUND:Polychlorinated biphenyls (PCBs) are environmental toxicants; PCB exposure has been associated with adverse effects on wildlife and humans. However, the mechanisms underlying these adverse effects are not fully understood. The steroid and xenobiotic receptor [SXR; also known as the pregnane X receptor (PXR) and formally known as NR1I2] is a nuclear hormone receptor that regulates inducible metabolism of drugs and xenobiotics and is activated or inhibited by various PCB congeners. OBJECTIVES:The aim of this study was to investigate the effects of exposure to PCB-153, the most prevalent PCB congener in human tissues, on SXR knockout mice (SXRKO) and to elucidate the role of SXR in PCB-153 metabolism and promotion of its harmful effects. METHODS:Wild-type (WT) and SXRKO mice were chronically or perinatally exposed to a low dose (54μg/kg/d) of PCB-153. Blood, livers, and spleens were analyzed using transcriptome sequencing (RNA-seq) and molecular techniques to investigate the impacts of exposure on metabolism, oxidative stress, and hematological parameters. RESULTS:SXRKO mice perinatally exposed to PCB-153 displayed elevated oxidative stress, symptoms of hemolytic anemia, and premature death. Transcriptomal analysis revealed that expression of genes involved in metabolic processes was altered in SXRKO mice. Elevated levels of the PCB-153 metabolite, 3-OH-PCB-153, were found in exposed SXRKO mice compared to exposed WT mice. Blood hemoglobin (HGB) levels were lower throughout the lifespan, and the occurrence of intestinal tumors was larger in SXRKO mice chronically exposed to PCB-153 compared to vehicle and WT controls. DISCUSSION:Our results suggest that altered metabolism induced by SXR loss of function resulted in the accumulation of hydroxylated metabolites upon exposure to PCB-153, leading to oxidative stress, hemolytic anemia, and tumor development in a mouse model. These results support a major role for SXR/PXR in protection against xenobiotic-induced oxidative stress by maintaining proper metabolism in response to PCB-153 exposure. This role of SXR could be generally applicable to other environmental toxicants as well as pharmaceutical drugs. https://doi.org/10.1289/EHP6262.

Dataset Information

Chalinulasterol, a chlorinated steroid disulfate from the Caribbean sponge Chalinula molitba. Evaluation of its role as PXR receptor modulator.

Publications

Chalinulasterol, a chlorinated steroid disulfate from the Caribbean sponge Chalinula molitba. Evaluation of its role as PXR receptor modulator.

Similar Datasets

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