Toxicogenomic Analysis of Mainstream Tobacco Smoke-Exposed Mice Reveals Repression of Plasminogen Activator Inhibitor-1 Gene in Heart

Figures & data

TABLE 1  List of genes up or down regulated in the treatment groups

Description (Mus musculus mRNA)	Fold change
	1	2	3	4
Cytochrome P-450, family 1, subfamily a, polypeptide 1 (Cyp1a1)	11.7	1.3	8.2	−1.0
Cysteine-rich protein 61 (Cyr61)	−1.9	−1.3	−1.1	−1.4
RIKEN cDNA 1300002F13 gene (1300002F13Rik)	−1.8	−1.4	−1.0	−1.3
H2A histone family, member Y (H2afy)	1.8	−1.2	1.1	1.0
Serine (or cysteine) proteinase inhibitor, clade E, member 1 (Serpine1)	−1.7	−1.5	−1.3	−1.5
DNA segment, Chr 4, expressed (D4Wsu53e)	1.6	1.1	1.2	1.1
Basic helix–loop–helix domain containing, class B2 (Bhlhb2)	−1.5	−1.2	−1.1	−1.2
Karyopherin (importin) alpha 2 (Kpna2)	1.5	1.1	1.0	1.0
Small proline-rich protein 1A (Sprr1a)	−1.5	1.2	−1.0	−1.2
Lipin 3 (Lpin3)	−1.4	1.2	−1.0	−1.1
Colony-stimulating factor 1 (macrophage) (Csf1)	−1.4	1.0	−1.1	−1.0
Unknown	−1.3	1.1	1.0	−1.1
A kinase (PRKA) anchor protein (gravin) 12 (Akap12)	−1.3	1.0	−1.0	−1.1
Carbamoyl-phosphate synthetase 1	−1.1	−1.3	1.3	1.3
RIKEN cDNA 4632404H22 gene (4632404H22Rik)	−1.2	−1.2	1.3	−1.1

Note. Fold induction over matched controls for treatment groups: 1, 6 wk smoke; 2, 6 wk smoke followed by 6 wk break; 3, 12 wk smoke; 4, 12 wk smoke followed by 6 wk break. Negative values indicate downregulated genes.

FIG. 1  Validation of microarray results. Data are presented as fold change over control values (n = 5 mice/group, ± SEM): 1, 6 wk smoke; 2, 6 wk smoke + 6 wk break; 3, 12 wk smoke; and 4, 12 wk smoke + 6 wk break. Asterisk indicates significant at p< .05, t-test conducted on RT-PCR values.

FIG. 2  Cyp1A1 protein abundance in heart microsome extract (n= 5). MW: molecular weight marker; +ve control: BaP-treated lung microsome extract. Lanes 1–4: treatment groups, 6 wk smoke, 12 wk smoke, 6 wk smoke + 6 wk break, and 12 wk smoke + 6 wk break; lanes 5–8: matched controls.

FIG. 3  (A) Total immunoreactive PAI-1 in heart tissue extracts. (B) PAI-1 activity in heart tissue extracts. Data represent fold change over matched controls (n= 5, ± SEM): 1, 6 wk smoke; 2, 6 wk smoke + 6 wk break; 3, 12 wk smoke; 4, 12 wk smoke + 6 wk break.

FIG. 4  (A) Western blot of immunoreactive tPA in heart tissue extracts. Lanes 1, 3, 5, and 7 represent 6 wk smoke, 6 wk smoke + 6 wk break, 12 wk smoke, and 12 wk smoke + 6 wk smoke. Lanes 2, 4, 6, and 8 represent matched controls. (B) Total tPA activity present in heart tissue extracts. Data shown as fold change over matched controls:1, 6 wk smoke; 2, 6 wk smoke + 6 wk break; 3, 12 wk smoke; 4, 12 wk smoke + 6 wk break.