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Dietary cadmium exposure causes elevation of blood ApoE with triglyceride level in mice

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Abstract

Cadmium (Cd) is a widespread toxic occupational and environmental pollutant, and its effect on lipid metabolism dysregulation has been observed. In this study, we utilized two-dimensional electrophoresis (2-DE) and mass spectrometry (MS) technologies to explore changes in the blood plasma proteins of mice exposed to Cd. From the 2-DE, 8 protein spots were screened in response to Cd exposure, and the identities of these proteins were revealed by MALDI-TOF MS. Western blotting was applied to analyze the expression of the apolipoproteins in both plasma and liver, which were consistent with Cd-induced dyslipidemia of their composed lipid. Moreover, the Cd-induced apolipoprotein ApoE upregulation was due to inhibition of autopahgic flux in the Cd exposed mice. It was further observed from the mouse liver that Cd reduced the expression of the lipid uptake receptor low-density lipoprotein receptor (LDLR), which might be responsible for the coordinated elevation in blood triglycerides and abnormal apolipoproteins. This study may provide a new insight into the mechanism of Cd-induced dyslipidemia and the risk of cardiovascular diseases.

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Abbreviations

2-DE:

Two-dimensional electrophoresis

ABCA1:

ATP-binding cassette transporter A1

AD:

Alzheimer’s disease

Apcs:

Amyloid P-component precursor

ApoA1p:

Apolipoprotein A-I precursor

ApoA2:

Apolipoprotein A-II

ApoA4:

Apolipoprotein A-IV

ApoC3p:

Apolipoprotein C-III precursor

ApoE:

Apolipoprotein E

Cd:

Cadmium

FFA:

Free (non-esterified) fatty acids

HDL-C:

High density lipoprotein-cholesterol

IEF:

Isoelectric focusing

LDL-C:

Low density lipoprotein-cholesterol

LDLR:

Low-density lipoprotein receptor

MTTP:

Microsomal triglyceride transfer protein

MS:

Mass spectrometry

PZP:

Pregnancy zone protein

PL:

Phospholipids

RBP:

Retinol-binding protein

TC:

Total cholesterol

TG:

Total triglycerides

VLDL-C:

Very low density lipoprotein-cholesterol

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (31600952 and 31271272) and the Start-Up Research Funding of Jiangsu University for Distinguished Scholars (5501330001). We thank the animal house staff for their care of the animals, and Ms. Ye Pan for technical assistance with the 2-D gel analysis.

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HL, YW, ZR, XJ and SD performed the research; JG and HS designed the research study and contributed essential reagents or tools; HL, YW, ZR, XJ, XZ, SD, YZ, JG and HS analyzed and interpreted the data; HL, YW, ZR, XJ, Frank, SD, JG and HS wrote the manuscript. All authors reviewed the manuscript.

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Correspondence to Jie Gu or Haifeng Shi.

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Liu, H., Wang, Y., Ren, Z. et al. Dietary cadmium exposure causes elevation of blood ApoE with triglyceride level in mice. Biometals 33, 241–254 (2020). https://doi.org/10.1007/s10534-020-00247-z

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