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Bach1 gene ablation reduces steatohepatitis in mouse MCD diet model.

Inoue M, Tazuma S, Kanno K, Hyogo H, Igarashi K, Chayama K - J Clin Biochem Nutr (2010)

Bottom Line: Since oxidative stress plays a pivotal role in the pathogenesis of nonalcoholic steatohepatitis (NASH), HO-1 induction would be expected to prevent the development of NASH.Bach1 ablation resulted in significant induction of HO-1 mRNA and its activity in the liver.These findings suggest that Bach1 ablation exerts hepatoprotective effect against steatohepatitis presumably via HO-1 induction and may be a potential therapeutic target.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.

ABSTRACT
Bach1 is a transcriptional repressor of heme oxygenase-1 (HO-1, a.k.a. HSP-32), which is an inducible enzyme and has anti-oxidation/anti-inflammatory properties shown in various models of organ injuries. Since oxidative stress plays a pivotal role in the pathogenesis of nonalcoholic steatohepatitis (NASH), HO-1 induction would be expected to prevent the development of NASH. In this study, we investigated the influence of Bach1 ablation in mice on the progression of NASH in methionine-choline deficient (MCD) diet model. Bach1 ablation resulted in significant induction of HO-1 mRNA and its activity in the liver. When fed MCD diet, Bach1(-/-) mice exhibited negligible hepatic steatosis compared to pronounced steatohepatitis in wild type mice with 6-fold increase in hepatic triglyceride content. Whereas feeding of MCD diet decreased mRNA expressions of peroxisome proliferator-activated receptor (PPAR) α and microsomal triglyceride transfer protein (MTP) in wild type mice, there were no change in Bach1(-/-) mice. In addition, hepatic concentration of malondialdehyde (MDA), a biomarker for oxidative stress as well as plasma alanine aminotransferase (ALT) was significantly lower in Bach1(-/-) mice. These findings suggest that Bach1 ablation exerts hepatoprotective effect against steatohepatitis presumably via HO-1 induction and may be a potential therapeutic target.

No MeSH data available.


Related in: MedlinePlus

Hepatic HO-1 expression and its activity in the absence of Bach1. (A) Wild type mice (open bar) and Bach1−/− mice (closed bar) were fed either regular chow or MCD diet for 8 w prior to quantification of hepatic expression of HO-1 mRNA by real-time PCR (n = 5/each group). (B) HO-1 activity in the liver from wild type (WT) or Bach1−/− (KO) mice were determined with standardlized of protein concentration (n = 5/each group). ZnPP was utilized as a HO-1 inhibitor for negative control. *p<0.05, wild type vs Bach1−/− mice.
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Figure 1: Hepatic HO-1 expression and its activity in the absence of Bach1. (A) Wild type mice (open bar) and Bach1−/− mice (closed bar) were fed either regular chow or MCD diet for 8 w prior to quantification of hepatic expression of HO-1 mRNA by real-time PCR (n = 5/each group). (B) HO-1 activity in the liver from wild type (WT) or Bach1−/− (KO) mice were determined with standardlized of protein concentration (n = 5/each group). ZnPP was utilized as a HO-1 inhibitor for negative control. *p<0.05, wild type vs Bach1−/− mice.

Mentions: Fig. 1 demonstrates the regulation of HO-1 expression and its activity by Bach1. As shown in Fig. 1A, real-time PCR quantified a 8-fold up-regulation of HO-1 mRNA in Bach1−/− mice on chow diet. Despite not being statistically significant, there was 2-fold up-regulation of mRNA by MCD diet in wild type mice. Consistent with these changes in mRNA expressions, Fig. 1B demonstrates 5-fold increase in hepatic HO-1 activity in the absence of Bach1, which was entirely repressed by intraperitoneal injection of ZnPP, an HO-1 inhibitor.


Bach1 gene ablation reduces steatohepatitis in mouse MCD diet model.

Inoue M, Tazuma S, Kanno K, Hyogo H, Igarashi K, Chayama K - J Clin Biochem Nutr (2010)

Hepatic HO-1 expression and its activity in the absence of Bach1. (A) Wild type mice (open bar) and Bach1−/− mice (closed bar) were fed either regular chow or MCD diet for 8 w prior to quantification of hepatic expression of HO-1 mRNA by real-time PCR (n = 5/each group). (B) HO-1 activity in the liver from wild type (WT) or Bach1−/− (KO) mice were determined with standardlized of protein concentration (n = 5/each group). ZnPP was utilized as a HO-1 inhibitor for negative control. *p<0.05, wild type vs Bach1−/− mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3045690&req=5

Figure 1: Hepatic HO-1 expression and its activity in the absence of Bach1. (A) Wild type mice (open bar) and Bach1−/− mice (closed bar) were fed either regular chow or MCD diet for 8 w prior to quantification of hepatic expression of HO-1 mRNA by real-time PCR (n = 5/each group). (B) HO-1 activity in the liver from wild type (WT) or Bach1−/− (KO) mice were determined with standardlized of protein concentration (n = 5/each group). ZnPP was utilized as a HO-1 inhibitor for negative control. *p<0.05, wild type vs Bach1−/− mice.
Mentions: Fig. 1 demonstrates the regulation of HO-1 expression and its activity by Bach1. As shown in Fig. 1A, real-time PCR quantified a 8-fold up-regulation of HO-1 mRNA in Bach1−/− mice on chow diet. Despite not being statistically significant, there was 2-fold up-regulation of mRNA by MCD diet in wild type mice. Consistent with these changes in mRNA expressions, Fig. 1B demonstrates 5-fold increase in hepatic HO-1 activity in the absence of Bach1, which was entirely repressed by intraperitoneal injection of ZnPP, an HO-1 inhibitor.

Bottom Line: Since oxidative stress plays a pivotal role in the pathogenesis of nonalcoholic steatohepatitis (NASH), HO-1 induction would be expected to prevent the development of NASH.Bach1 ablation resulted in significant induction of HO-1 mRNA and its activity in the liver.These findings suggest that Bach1 ablation exerts hepatoprotective effect against steatohepatitis presumably via HO-1 induction and may be a potential therapeutic target.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.

ABSTRACT
Bach1 is a transcriptional repressor of heme oxygenase-1 (HO-1, a.k.a. HSP-32), which is an inducible enzyme and has anti-oxidation/anti-inflammatory properties shown in various models of organ injuries. Since oxidative stress plays a pivotal role in the pathogenesis of nonalcoholic steatohepatitis (NASH), HO-1 induction would be expected to prevent the development of NASH. In this study, we investigated the influence of Bach1 ablation in mice on the progression of NASH in methionine-choline deficient (MCD) diet model. Bach1 ablation resulted in significant induction of HO-1 mRNA and its activity in the liver. When fed MCD diet, Bach1(-/-) mice exhibited negligible hepatic steatosis compared to pronounced steatohepatitis in wild type mice with 6-fold increase in hepatic triglyceride content. Whereas feeding of MCD diet decreased mRNA expressions of peroxisome proliferator-activated receptor (PPAR) α and microsomal triglyceride transfer protein (MTP) in wild type mice, there were no change in Bach1(-/-) mice. In addition, hepatic concentration of malondialdehyde (MDA), a biomarker for oxidative stress as well as plasma alanine aminotransferase (ALT) was significantly lower in Bach1(-/-) mice. These findings suggest that Bach1 ablation exerts hepatoprotective effect against steatohepatitis presumably via HO-1 induction and may be a potential therapeutic target.

No MeSH data available.


Related in: MedlinePlus