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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

Protective effect of Bach1 ablation on MCD diet-induced liver injury. (A) Serum ALT levels were determined at indicated time points by 8 w in wild type mice and Bach1−/− mice fed either regular chow or MCD diet (n = 5/each group). (B) Hepatic MDA concentration was assessed with standarlization of protein concentration in wild type (open bar) and Bach1−/− (closed bar) mice (n = 5/each group). *p<0.05, regular chow vs MCD diet. †p<0.05, wild type vs Bach1−/− mice.
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Figure 3: Protective effect of Bach1 ablation on MCD diet-induced liver injury. (A) Serum ALT levels were determined at indicated time points by 8 w in wild type mice and Bach1−/− mice fed either regular chow or MCD diet (n = 5/each group). (B) Hepatic MDA concentration was assessed with standarlization of protein concentration in wild type (open bar) and Bach1−/− (closed bar) mice (n = 5/each group). *p<0.05, regular chow vs MCD diet. †p<0.05, wild type vs Bach1−/− mice.

Mentions: Feeding of MCD diet increased serum ALT levels in wild type mice at 4 and 8 weeks whereas it remained the basal level in Bach1−/− mice, implying protective effect of Bach1 ablation against liver injury (Fig. 3A). Consistent with these findings, hepatic MDA concentration which reflects oxidative damage elicited by lipid peroxidation in the liver remained unchanged in Bach1−/− mice following MCD diet (Fig. 3B). This was in marked contrast to 4-fold increase in MDA level in wild type mice on MCD diet.


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)

Protective effect of Bach1 ablation on MCD diet-induced liver injury. (A) Serum ALT levels were determined at indicated time points by 8 w in wild type mice and Bach1−/− mice fed either regular chow or MCD diet (n = 5/each group). (B) Hepatic MDA concentration was assessed with standarlization of protein concentration in wild type (open bar) and Bach1−/− (closed bar) mice (n = 5/each group). *p<0.05, regular chow vs MCD diet. †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 3: Protective effect of Bach1 ablation on MCD diet-induced liver injury. (A) Serum ALT levels were determined at indicated time points by 8 w in wild type mice and Bach1−/− mice fed either regular chow or MCD diet (n = 5/each group). (B) Hepatic MDA concentration was assessed with standarlization of protein concentration in wild type (open bar) and Bach1−/− (closed bar) mice (n = 5/each group). *p<0.05, regular chow vs MCD diet. †p<0.05, wild type vs Bach1−/− mice.
Mentions: Feeding of MCD diet increased serum ALT levels in wild type mice at 4 and 8 weeks whereas it remained the basal level in Bach1−/− mice, implying protective effect of Bach1 ablation against liver injury (Fig. 3A). Consistent with these findings, hepatic MDA concentration which reflects oxidative damage elicited by lipid peroxidation in the liver remained unchanged in Bach1−/− mice following MCD diet (Fig. 3B). This was in marked contrast to 4-fold increase in MDA level in wild type mice on MCD diet.

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