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Effects of chronic cadmium exposure on brain and liver transporters and drug-metabolizing enzymes in male and female mice genetically predisposed to Alzheimer's disease

Hao Wang, Liang Zhang, Zhengui Xia and Julia Yue Cui
Drug Metabolism and Disposition July 25, 2022, DMD-AR-2021-000453; DOI: https://doi.org/10.1124/dmd.121.000453

Data Supplement

  • Supplemental Table 1 -

    Supplementary Table 1: Expression levels of transporter genes in mice brains and livers among different groups.

  • Supplemental Table 2 -

    Supplementary Table 2: Differentially expressed transporter genes (BH-FDR < 0.05) in brains by Cd exposure among different mice groups.

  • Supplemental Table 3 -

    Supplementary Table 3: Differentially expressed transporter genes (BH-FDR < 0.05) in livers by Cd exposure among different mice groups.

  • Supplemental Table 4 -

    Supplementary Table 4: Primers used in RT-PCR

  • Supplemental Figures -

    Supplementary Figure 1: Gene ontology (GO) enrichment analysis of differentially regulated genes. Up-regulated gene ontology enrichment terms in brains for ApoE3 male, ApoE3 female,  ApoE4 male, and ApoE4 female mice. The blue dotted line represents -log10(FDR) = 1.3. n = 3 in each group.

    Supplementary Figure 2: The basal expression levels of transporters in brains and livers across different mice groups. (A) ATP-binding cassette (Abc) family. (B) Organic anion transporting polypeptide (Oatp/Slco) family. (C) The remaining solute carrier (Slc) superfamily except SLCO family. (D) The remaining ATPase superfamily except Abc transporters. n = 3 in each group. Data are presented as mean ± SEM, and compared between brain and liver in each group. **p<0.005;
    ***p<0.001.

    Supplementary Figure 3: RT-qPCR of selected genes in livers of male and female ApoE3 and ApoE4 mice following exposure to vehicle and Cd treatment. Data are expressed as % of the house keeping gene. (n=4-5/sex/genotype/exposure) were analyzed using three-way analysis of variance (ANOVA) considering the effects of sex ($), genotype (#), and exposure (*). Data are presented as mean ± SEM. */$/#p <0.05; **/$$/##p<0.005; ***/$$$/###p<0.001.

    Supplementary Figure 4: RT-qPCR of selected genes in brains of male and female ApoE3 and ApoE4 mice following exposure to vehicle and Cd treatment. Data are expressed as % of the housekeeping gene. (n=4- 5/sex/genotype/exposure) were analyzed using three-way analysis of variance (ANOVA) considering the effects of sex ($), genotype (#), and exposure (*). Data are presented as mean ± SEM. */$/#p <0.05; **/$$/##p<0.005; ***/$$$/###p<0.001.

    Supplementary Figure 5: Protein expression of Slc38a4 in livers of male and female ApoE3 and ApoE4 mice following exposure to vehicle and Cd treatment. n = 3 in each group. Data are presented as mean ± SEM.

    Supplementary Figure 6: Protein expression of Slc38a3 and Slc40a1 in livers of male and female ApoE3 and ApoE4 mice following exposure to vehicle and Cd treatment. n = 3 in each group. Data are presented as mean ± SEM.

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