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Binding of PFOS to serum albumin and DNA: insight into the molecular toxicity of perfluorochemicals.

Zhang X, Chen L, Fei XC, Ma YS, Gao HW - BMC Mol. Biol. (2009)

Bottom Line: ITC results showed that all the interactions were spontaneous driven by entropy change.At normal physiological conditions, 1.2 mmol/l PFOS reduces the binding ratio of Vitamin B2 to SA by more than 30%.This work provides a useful experimental method for further studying the toxigenicity of PFCs.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, PR China. zhangwxian1001@yahoo.com.cn

ABSTRACT

Background: Health risk from exposure of perfluorochemicals (PFCs) to wildlife and human has been a subject of great interest for understanding their molecular mechanism of toxicity. Although much work has been done, the toxigenicity of PFCs remains largely unknown. In this work, the non-covalent interactions between perfluorooctane sulfonate (PFOS) and serum albumin (SA) and DNA were investigated under normal physiological conditions, aiming to elucidate the toxigenicity of PFCs.

Results: In equilibrium dialysis assay, the bindings of PFOS to SA correspond to the Langmuir isothermal model with two-step sequence model. The saturation binding number of PFOS was 45 per molecule of SA and 1 per three base-pairs of DNA, respectively. ITC results showed that all the interactions were spontaneous driven by entropy change. Static quenching of the fluorescence of SA was observed when interacting with PFOS, indicating PFOS bound Trp residue of SA. CD spectra of SA and DNA changed obviously in the presence of PFOS. At normal physiological conditions, 1.2 mmol/l PFOS reduces the binding ratio of Vitamin B2 to SA by more than 30%.

Conclusion: The ion bond, van der Waals force and hydrophobic interaction contributed to PFOS binding to peptide chain of SA and to the groove bases of DNA duplex. The non-covalent interactions of PFOS with SA and DNA alter their secondary conformations, with the physiological function of SA to transport Vitamin B2 being inhibited consequently. This work provides a useful experimental method for further studying the toxigenicity of PFCs.

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Effects of pH (A), electrolyte (B) and temperature (C) on γ of solutions containing 0.8 mmol/l PFOS, 0.016 mmol/l SA (A and B) and 0.02 mmol/l SA (C), 0.9 mmol/l DNA (A) and 1.19 mmol/l DNA (B and C).
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Figure 2: Effects of pH (A), electrolyte (B) and temperature (C) on γ of solutions containing 0.8 mmol/l PFOS, 0.016 mmol/l SA (A and B) and 0.02 mmol/l SA (C), 0.9 mmol/l DNA (A) and 1.19 mmol/l DNA (B and C).

Mentions: The stability of non-covalent interaction is always affected by various environmental conditions such as pH, ionic strength and temperature [71,72]. As is shown in Fig. 2A, γ for the PFOS-SA binding decreases obviously with increasing pH. It implies that the acidic media are more favorable for PFOS binding to SA. As we know from the dissociation constants (KR) of the side groups (R) of basic and acidic AARs of SA, more side groups (R) of AARs are protonated and positively charged in acidic media. Thus, the electrostatic attraction between the sulfonic acid head of PFOS and the positively charged AARs will be much stronger than that in neutral media [67,68], which result in the increasing of binding number of PFOS to SA. Moreover, SA tends to unfold in acidic media, so steric hindrance decreases, leading to an increasing of possible binding sites as well as the binding number. As to DNA, increasing binding is obviously observed at pH 2. Similar to SA, DNA tends to unfold in acidic media, too. The increasing of possible binding sites resulting from the unfolding of DNA may be the reason that PFOS-DNA binding number increases. In addition, a peak of γ appears at pH 7.4 for the PFOS-DNA binding and then γ decreases at pH 8.4 and 9.4 afterwards. It implies the neutral media is comparatively more favorable for PFOS binding, indicating the potential risk of PFOS toxicity under the physiological condition of wildlife and human.


Binding of PFOS to serum albumin and DNA: insight into the molecular toxicity of perfluorochemicals.

Zhang X, Chen L, Fei XC, Ma YS, Gao HW - BMC Mol. Biol. (2009)

Effects of pH (A), electrolyte (B) and temperature (C) on γ of solutions containing 0.8 mmol/l PFOS, 0.016 mmol/l SA (A and B) and 0.02 mmol/l SA (C), 0.9 mmol/l DNA (A) and 1.19 mmol/l DNA (B and C).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2656506&req=5

Figure 2: Effects of pH (A), electrolyte (B) and temperature (C) on γ of solutions containing 0.8 mmol/l PFOS, 0.016 mmol/l SA (A and B) and 0.02 mmol/l SA (C), 0.9 mmol/l DNA (A) and 1.19 mmol/l DNA (B and C).
Mentions: The stability of non-covalent interaction is always affected by various environmental conditions such as pH, ionic strength and temperature [71,72]. As is shown in Fig. 2A, γ for the PFOS-SA binding decreases obviously with increasing pH. It implies that the acidic media are more favorable for PFOS binding to SA. As we know from the dissociation constants (KR) of the side groups (R) of basic and acidic AARs of SA, more side groups (R) of AARs are protonated and positively charged in acidic media. Thus, the electrostatic attraction between the sulfonic acid head of PFOS and the positively charged AARs will be much stronger than that in neutral media [67,68], which result in the increasing of binding number of PFOS to SA. Moreover, SA tends to unfold in acidic media, so steric hindrance decreases, leading to an increasing of possible binding sites as well as the binding number. As to DNA, increasing binding is obviously observed at pH 2. Similar to SA, DNA tends to unfold in acidic media, too. The increasing of possible binding sites resulting from the unfolding of DNA may be the reason that PFOS-DNA binding number increases. In addition, a peak of γ appears at pH 7.4 for the PFOS-DNA binding and then γ decreases at pH 8.4 and 9.4 afterwards. It implies the neutral media is comparatively more favorable for PFOS binding, indicating the potential risk of PFOS toxicity under the physiological condition of wildlife and human.

Bottom Line: ITC results showed that all the interactions were spontaneous driven by entropy change.At normal physiological conditions, 1.2 mmol/l PFOS reduces the binding ratio of Vitamin B2 to SA by more than 30%.This work provides a useful experimental method for further studying the toxigenicity of PFCs.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, PR China. zhangwxian1001@yahoo.com.cn

ABSTRACT

Background: Health risk from exposure of perfluorochemicals (PFCs) to wildlife and human has been a subject of great interest for understanding their molecular mechanism of toxicity. Although much work has been done, the toxigenicity of PFCs remains largely unknown. In this work, the non-covalent interactions between perfluorooctane sulfonate (PFOS) and serum albumin (SA) and DNA were investigated under normal physiological conditions, aiming to elucidate the toxigenicity of PFCs.

Results: In equilibrium dialysis assay, the bindings of PFOS to SA correspond to the Langmuir isothermal model with two-step sequence model. The saturation binding number of PFOS was 45 per molecule of SA and 1 per three base-pairs of DNA, respectively. ITC results showed that all the interactions were spontaneous driven by entropy change. Static quenching of the fluorescence of SA was observed when interacting with PFOS, indicating PFOS bound Trp residue of SA. CD spectra of SA and DNA changed obviously in the presence of PFOS. At normal physiological conditions, 1.2 mmol/l PFOS reduces the binding ratio of Vitamin B2 to SA by more than 30%.

Conclusion: The ion bond, van der Waals force and hydrophobic interaction contributed to PFOS binding to peptide chain of SA and to the groove bases of DNA duplex. The non-covalent interactions of PFOS with SA and DNA alter their secondary conformations, with the physiological function of SA to transport Vitamin B2 being inhibited consequently. This work provides a useful experimental method for further studying the toxigenicity of PFCs.

Show MeSH
Related in: MedlinePlus