Limits...
Downregulation in GATA4 and Downstream Structural and Contractile Genes in the db/db Mouse Heart.

Broderick TL, Jankowski M, Wang D, Danalache BA, Parrott CR, Gutkowska J - ISRN Endocrinol (2012)

Bottom Line: Reduced expression of GATA4, a transcriptional factor for structural and cardioprotective genes, has been proposed as a factor contributing to the development of cardiomyopathy.CHIP protein content was modestly downregulated (27%) in db/db mice whereas mRNA and protein expression of the CHIP cochaperone HSP70 was significantly decreased in db/db hearts.Our results indicate that low GATA4 in db/db mouse heart is accompanied by reduced expression of GATA4-regulated cardioprotective and structural genes, which may explain the development of cardiomyopathy in diabetes.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Diabetes and Exercise Metabolism, Department of Physiology, Midwestern University, 19555 North 59th Avenue, Glendale, AZ, 85308, USA.

ABSTRACT
Reduced expression of GATA4, a transcriptional factor for structural and cardioprotective genes, has been proposed as a factor contributing to the development of cardiomyopathy. We investigated whether the reduction of cardiac GATA4 expression reported in diabetes alters the expression of downstream genes, namely, atrial natriuretic peptide (ANP), B-type natriuretic, peptide (BNP), and α- and β-myosin heavy chain (MHC). db/db mice, a model of type 2 diabetes, with lean littermates serving as controls, were studied. db/db mice exhibited obesity, hyperglycemia, and reduced protein expression of cardiac GLUT4 and IRAP (insulin-regulated aminopeptidase), the structural protein cosecreted with GLUT4. Hearts from db/db mice had reduced protein expression of GATA4 (~35%) with accompanying reductions in mRNA expression of ANP (~40%), BNP (~85%), and α-MHC mRNA (~50%) whereas expression of β-MHC mRNA was increased by ~60%. Low GATA4 was not explained by an increased ligase or atrogin1 expression. CHIP protein content was modestly downregulated (27%) in db/db mice whereas mRNA and protein expression of the CHIP cochaperone HSP70 was significantly decreased in db/db hearts. Our results indicate that low GATA4 in db/db mouse heart is accompanied by reduced expression of GATA4-regulated cardioprotective and structural genes, which may explain the development of cardiomyopathy in diabetes.

No MeSH data available.


Related in: MedlinePlus

Cardiac CHIP mRNA and protein expression (a, b), atrogin1 mRNA expression (c), and MuRF1 mRNA expression (d) in control and db/db mice. Values are expressed as mean ± SEM obtained from 2 separate experiments each performed with 5 hearts. db/+, control mice; db/db, diabetic mice.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3313578&req=5

fig6: Cardiac CHIP mRNA and protein expression (a, b), atrogin1 mRNA expression (c), and MuRF1 mRNA expression (d) in control and db/db mice. Values are expressed as mean ± SEM obtained from 2 separate experiments each performed with 5 hearts. db/+, control mice; db/db, diabetic mice.

Mentions: To investigate whether the decrease in GATA4 protein expression in hearts of db/db mice was the result of increased proteosome activity, expression of ubiquitin ligases of CHIP, MuRF1, and atrogin1 were measured. As illustrated in Figure 6, no significant differences between db/db and control hearts were observed in the expression of these ligases, although CHIP protein expression was decreased by 26% in db/db hearts. However, we measured the molecular chaperone HSP70 because of its association with CHIP, and as shown in Figure 7, both HSP70 mRNA and protein expression were decreased by 45% and 35%, respectively, in db/db hearts compared with control hearts (Figure 7).


Downregulation in GATA4 and Downstream Structural and Contractile Genes in the db/db Mouse Heart.

Broderick TL, Jankowski M, Wang D, Danalache BA, Parrott CR, Gutkowska J - ISRN Endocrinol (2012)

Cardiac CHIP mRNA and protein expression (a, b), atrogin1 mRNA expression (c), and MuRF1 mRNA expression (d) in control and db/db mice. Values are expressed as mean ± SEM obtained from 2 separate experiments each performed with 5 hearts. db/+, control mice; db/db, diabetic mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3313578&req=5

fig6: Cardiac CHIP mRNA and protein expression (a, b), atrogin1 mRNA expression (c), and MuRF1 mRNA expression (d) in control and db/db mice. Values are expressed as mean ± SEM obtained from 2 separate experiments each performed with 5 hearts. db/+, control mice; db/db, diabetic mice.
Mentions: To investigate whether the decrease in GATA4 protein expression in hearts of db/db mice was the result of increased proteosome activity, expression of ubiquitin ligases of CHIP, MuRF1, and atrogin1 were measured. As illustrated in Figure 6, no significant differences between db/db and control hearts were observed in the expression of these ligases, although CHIP protein expression was decreased by 26% in db/db hearts. However, we measured the molecular chaperone HSP70 because of its association with CHIP, and as shown in Figure 7, both HSP70 mRNA and protein expression were decreased by 45% and 35%, respectively, in db/db hearts compared with control hearts (Figure 7).

Bottom Line: Reduced expression of GATA4, a transcriptional factor for structural and cardioprotective genes, has been proposed as a factor contributing to the development of cardiomyopathy.CHIP protein content was modestly downregulated (27%) in db/db mice whereas mRNA and protein expression of the CHIP cochaperone HSP70 was significantly decreased in db/db hearts.Our results indicate that low GATA4 in db/db mouse heart is accompanied by reduced expression of GATA4-regulated cardioprotective and structural genes, which may explain the development of cardiomyopathy in diabetes.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Diabetes and Exercise Metabolism, Department of Physiology, Midwestern University, 19555 North 59th Avenue, Glendale, AZ, 85308, USA.

ABSTRACT
Reduced expression of GATA4, a transcriptional factor for structural and cardioprotective genes, has been proposed as a factor contributing to the development of cardiomyopathy. We investigated whether the reduction of cardiac GATA4 expression reported in diabetes alters the expression of downstream genes, namely, atrial natriuretic peptide (ANP), B-type natriuretic, peptide (BNP), and α- and β-myosin heavy chain (MHC). db/db mice, a model of type 2 diabetes, with lean littermates serving as controls, were studied. db/db mice exhibited obesity, hyperglycemia, and reduced protein expression of cardiac GLUT4 and IRAP (insulin-regulated aminopeptidase), the structural protein cosecreted with GLUT4. Hearts from db/db mice had reduced protein expression of GATA4 (~35%) with accompanying reductions in mRNA expression of ANP (~40%), BNP (~85%), and α-MHC mRNA (~50%) whereas expression of β-MHC mRNA was increased by ~60%. Low GATA4 was not explained by an increased ligase or atrogin1 expression. CHIP protein content was modestly downregulated (27%) in db/db mice whereas mRNA and protein expression of the CHIP cochaperone HSP70 was significantly decreased in db/db hearts. Our results indicate that low GATA4 in db/db mouse heart is accompanied by reduced expression of GATA4-regulated cardioprotective and structural genes, which may explain the development of cardiomyopathy in diabetes.

No MeSH data available.


Related in: MedlinePlus