Cytochrome c adducts with PCB quinoid metabolites

Abstract

PCBs are a group of 209 individual congeners widely used as industrial chemicals. PCBs are found as by-products in dye and paint manufacture and are legacy, ubiquitous and persistent as human and environmental contaminants. PCBs with fewer chlorine atoms may be metabolized to hydroxy- and dihydroxy- metabolites and further oxidized to quinoid metabolites both in vitro and in vivo. Specifically, quinoid metabolites may form adducts on nucleophilic sites within cells. We hypothesized that the PCB-quinones covalently bind to cytochrome c and thereby cause defects in the function of cytochrome c. In this study synthetic PCB quinones (2-(4’-chlorophenyl)-1,4-benzoquinone, 2-(3’, 5’-dichlorophenyl)-1,4-benzoquinone, 2-(3’,4’, 5’-trichlorophenyl)-1,4-benzoquinone, and 2-(4’-chlorophenyl)-3,6-dichloro-1,4-benzoquinone) were incubated with cytochrome c, and adducts were detected by LC-MS and MALDI TOF. SDS PAGE gel electrophoresis was employed to separate the adducted proteins, while trypsin digestion and LC-MS/MS were applied to identify the amino acid binding sites on cytochrome c. Conformation change of cytochrome c after binding with PCB3-para-quinone was investigated by SYBYL-X simulation and cytochrome c function was examined. We found that more than one molecule of PCB-quinone may bind to one molecule of cytochrome c. Lysine and glutamic acid were identified as the predominant binding sites. Software simulation showed conformation changes of adducted cytochrome c. Additionally, cross-linking of cytochrome c was observed on the SDS PAGE gel. Cytochrome c was found to be in the reduced form after incubation with PCB quinones. These data provide evidence that the covalent binding of PCB quinone metabolites to cytochrome c may be included among the toxic effects of PCBs.

Protein adducts and crosslinking by reactive metabolites of polychlorinated biphenyls (PCBs)

“…The results show that the PCB3-pQ has the ability to form protein crosslinks. The protein crosslinks formation by PCB quinoid metabolites were also reported in previous research (Bender et al 2006, Qin et al 2013, Li et al 2015).…”

“…Protein adducts from polychlorinated biphenyls (PCBs) or PCB metabolites were identified by different research studies both in vitro and in vivo. PCB quinone metabolites have been found to form a covalent bond with human hydroxysteroid sulfotransferase hSULT2A1 (Qin et al 2013), with cytochrome c through lysine residues (Li et al 2015), and with glutathione and topoisomerase II (Srinivasan et al 2002), which caused a decrease of enzyme activity or dysfunction of proteins. Using radioactive compounds, PCB3 and PCB77 were found covalently bound to nuclear proteins in liver in vivo (Pereg et al 2001), and they were also shown to form hemoglobin adducts in vivo (Tampal et al 2003).…”

Amoxicillin Extraction from Aqueous Solution by Emulsion Liquid Membranes Using Response Surface Methodology

“…The parameters and experimental conditions are given in Tab. 1. The values of a number of parameters such as feed concentration, carrier concentration, internal phase concentration, and treat ratio were varied during the extraction tests to observe their effects on AMX separation.…”

“…In recent years, much attention has been paid to research considering the reduction of water pollutants with significant studies on this issue [1][2][3]. The presence of these compounds in the environment leads to extensive microbial and chemical damages to the ecosystem exposed to wastewater [4].…”

A novel chemiluminescence sensor for the determination of indomethacin based on sulfur and nitrogen co‐doped carbon quantum dot–KMnO4 reaction

“…Furthermore, indomethacin and other NSAIDs are increasingly used in large amounts in human (and veterinary) medicine around the world, and despite sewage and wastewater treatment systems, many incompletely removed pharmaceuticals are released to the environment. Because of their harmful effects on humans and other organisms, pharmaceutical residues have attracted public attention [2,3] and various analytical methods have been used to monitor them in the environment.…”