当前位置： SCI文献检索 > CHEMICAL RESEARCH IN TOXICOLOGY期刊下所有文献 > Differential cellular responses to protein adducts of naphthoquinone and monocrotaline pyrrole.

Differential cellular responses to protein adducts of naphthoquinone and monocrotaline pyrrole.

Abstract：

:Protein-xenobiotic adducts are byproducts of xenobiotic metabolism. While there is a correlation between protein adduction and target organ toxicity, a cause and effect relationship is not often clear. Naphthoquinone (NQ) and monocrotaline pyrrole (MCTP) are two pneumotoxic electrophiles that form covalent adducts with a similar select group of proteins rich in reactive thiols. In this study, we treated human pulmonary artery endothelial cells (HPAEC) with NQ, MCTP, or preformed NQ or MCTP adducts to the protein galectin-1 (gal-1) and examined indicators of reactive oxygen species (ROS) oxidative injury, markers of apoptosis (caspase-3 and annexin V), and gene responses of cellular stress. ROS production was assayed fluorescently using CM-H(2)DCFDA. NQ adducts to gal-1 (NQ-gal) produced 183% more intracellular ROS than gal-1 alone (p < 0.0001). Caspase-3 activity and annexin V staining of phosphatidylserine were used to assess apoptotic activity in treated cells. HPAEC exposed to MCTP-gal had increases in both caspase-3 activation and membrane translocation of annexin V relative to gal-1 alone (p < 0.0001). Direct application of NQ produced significantly more ROS and induced significant caspase-3 activation, whereas MCTP did not. Human bronchial epithelial cells were also exposed to MCTP-gal and found to have significant increases in both caspase-3 activation and annexin V staining in comparison to that of gal-1 (p < 0.05). Western blot analysis showed that both NQ and MCTP significantly induced the Nrf2 mediated stress response pathway despite differences in ROS generation. ER stress was not induced by either adducts or parent compounds as seen by quantitative RT-PCR, but HOX-1 expression was significantly induced by NQ-gal and MCTP alone. Electrophile adduction to gal-1 produces different cytotoxic effects specific to each reactive intermediate.

journal_name

Chem Res Toxicol

journal_title

Chemical research in toxicology

authors

Nakayama Wong LS,Lamé MW,Jones AD,Wilson DW

doi

10.1021/tx1002436

subject

Has Abstract

pub_date

2010-09-20 00:00:00

pages

1504-13

issue

eissn

0893-228X

issn

1520-5010

journal_volume

pub_type

杂志文章

在线工具

Differential cellular responses to protein adducts of naphthoquinone and monocrotaline pyrrole.