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Heme oxygenase-1: a novel therapeutic target for gastrointestinal diseases.

Naito Y, Takagi T, Uchiyama K, Yoshikawa T - J Clin Biochem Nutr (2011)

Bottom Line: Recent studies suggest that the induction of HO-1 expression plays a critical protective role in intestinal damage models induced by ischemia-reperfusion, indomethacin, lipopolysaccharide-associated sepsis, trinitrobenzene sulfonic acid, and dextran sulfate sodium, indicating that activation of HO-1 may act as an endogenous defensive mechanism to reduce inflammation and tissue injury in the gastrointestinal tract.In addition, CO derived from HO-1 is shown to be involved in the regulation in gastro-intestinal motility.These in vitro and in vivo data suggest that HO-1 may be a novel therapeutic target in patients with gastrointestinal diseases.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.

ABSTRACT
Heme oxygenase-1 (HO-1) is the rate-limiting enzyme in the catabolism of heme, followed by production of biliverdin, free iron and carbon monoxide (CO). HO-1 is a stress-responsive protein induced by various oxidative agents. Recent studies demonstrate that the expression of HO-1 in response to different inflammatory mediators may contribute to the resolution of inflammation and has protective effects in several organs against oxidative injury. Although the mechanism underlying the anti-inflammatory actions of HO-1 remains poorly defined, both CO and biliverdin/bilirubin have been implicated in this response. In the gastrointestinal tract, HO-1 is shown to be transcriptionally induced in response to oxidative stress, preconditioning and acute inflammation. Recent studies suggest that the induction of HO-1 expression plays a critical protective role in intestinal damage models induced by ischemia-reperfusion, indomethacin, lipopolysaccharide-associated sepsis, trinitrobenzene sulfonic acid, and dextran sulfate sodium, indicating that activation of HO-1 may act as an endogenous defensive mechanism to reduce inflammation and tissue injury in the gastrointestinal tract. In addition, CO derived from HO-1 is shown to be involved in the regulation in gastro-intestinal motility. These in vitro and in vivo data suggest that HO-1 may be a novel therapeutic target in patients with gastrointestinal diseases.

No MeSH data available.


Related in: MedlinePlus

(A) Effect of Bach1 deficiency on ulcer index in the intestinal mucosa treated with indomethacin. Data are expressed as means ± SEM of five to seven mice. (B) Macroscopic findings of the small intestine in mice treated with indomethacin. The administration of indomethacin provoked multiple erosions in the small intestine in wild type mice. On the other hand, in Bach1-deficient mice, the number and the severity of legions were clearly diminished.
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Figure 2: (A) Effect of Bach1 deficiency on ulcer index in the intestinal mucosa treated with indomethacin. Data are expressed as means ± SEM of five to seven mice. (B) Macroscopic findings of the small intestine in mice treated with indomethacin. The administration of indomethacin provoked multiple erosions in the small intestine in wild type mice. On the other hand, in Bach1-deficient mice, the number and the severity of legions were clearly diminished.

Mentions: Mice lacking the gene for Bach1 have dramatic increases in HO-1 expression in the heart, lung, liver, and gastro-intestinal tract, indicating a role for Bach1 in tonic suppression of HO-1 transcription. Bach1 deficiency ameliorates lipopolysaccharide-induced hepatic injury,(49) hyperoxic lung injury,(50) myocardial injury induced by ischemia-reperfusion,(51) hypertensive cardiopathy,(52) spinal cord injury,(53) indomethacin-induced intestinal injury,(54) and atherosclerosis in apolipoprotein E.(55) Recently, we have investigated the role of Bach1 in the pathogenesis of indomethacin-induced intestinal injury using Bach1-deficient mice, which are kindly presented from Prof. Igarashi (Tohoku University, Japan).(56) We have shown that the indomethacin-induced intestinal injury is remarkably improved in Bach1-deficient mice (Fig. 2), and that the increased expression of inflammatory chemokines and myeloperoxidase activity in the intestinal mucosa is suppressed in Bach1-deficient mice, respectively.(54) In addition, these beneficial effects observed in Bach1-deficient mice are reversed by the cotreatment with an HO-1 inhibitor, SnPP, indicating that these effects are mediated by the HO-1 activity.


Heme oxygenase-1: a novel therapeutic target for gastrointestinal diseases.

Naito Y, Takagi T, Uchiyama K, Yoshikawa T - J Clin Biochem Nutr (2011)

(A) Effect of Bach1 deficiency on ulcer index in the intestinal mucosa treated with indomethacin. Data are expressed as means ± SEM of five to seven mice. (B) Macroscopic findings of the small intestine in mice treated with indomethacin. The administration of indomethacin provoked multiple erosions in the small intestine in wild type mice. On the other hand, in Bach1-deficient mice, the number and the severity of legions were clearly diminished.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3045685&req=5

Figure 2: (A) Effect of Bach1 deficiency on ulcer index in the intestinal mucosa treated with indomethacin. Data are expressed as means ± SEM of five to seven mice. (B) Macroscopic findings of the small intestine in mice treated with indomethacin. The administration of indomethacin provoked multiple erosions in the small intestine in wild type mice. On the other hand, in Bach1-deficient mice, the number and the severity of legions were clearly diminished.
Mentions: Mice lacking the gene for Bach1 have dramatic increases in HO-1 expression in the heart, lung, liver, and gastro-intestinal tract, indicating a role for Bach1 in tonic suppression of HO-1 transcription. Bach1 deficiency ameliorates lipopolysaccharide-induced hepatic injury,(49) hyperoxic lung injury,(50) myocardial injury induced by ischemia-reperfusion,(51) hypertensive cardiopathy,(52) spinal cord injury,(53) indomethacin-induced intestinal injury,(54) and atherosclerosis in apolipoprotein E.(55) Recently, we have investigated the role of Bach1 in the pathogenesis of indomethacin-induced intestinal injury using Bach1-deficient mice, which are kindly presented from Prof. Igarashi (Tohoku University, Japan).(56) We have shown that the indomethacin-induced intestinal injury is remarkably improved in Bach1-deficient mice (Fig. 2), and that the increased expression of inflammatory chemokines and myeloperoxidase activity in the intestinal mucosa is suppressed in Bach1-deficient mice, respectively.(54) In addition, these beneficial effects observed in Bach1-deficient mice are reversed by the cotreatment with an HO-1 inhibitor, SnPP, indicating that these effects are mediated by the HO-1 activity.

Bottom Line: Recent studies suggest that the induction of HO-1 expression plays a critical protective role in intestinal damage models induced by ischemia-reperfusion, indomethacin, lipopolysaccharide-associated sepsis, trinitrobenzene sulfonic acid, and dextran sulfate sodium, indicating that activation of HO-1 may act as an endogenous defensive mechanism to reduce inflammation and tissue injury in the gastrointestinal tract.In addition, CO derived from HO-1 is shown to be involved in the regulation in gastro-intestinal motility.These in vitro and in vivo data suggest that HO-1 may be a novel therapeutic target in patients with gastrointestinal diseases.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.

ABSTRACT
Heme oxygenase-1 (HO-1) is the rate-limiting enzyme in the catabolism of heme, followed by production of biliverdin, free iron and carbon monoxide (CO). HO-1 is a stress-responsive protein induced by various oxidative agents. Recent studies demonstrate that the expression of HO-1 in response to different inflammatory mediators may contribute to the resolution of inflammation and has protective effects in several organs against oxidative injury. Although the mechanism underlying the anti-inflammatory actions of HO-1 remains poorly defined, both CO and biliverdin/bilirubin have been implicated in this response. In the gastrointestinal tract, HO-1 is shown to be transcriptionally induced in response to oxidative stress, preconditioning and acute inflammation. Recent studies suggest that the induction of HO-1 expression plays a critical protective role in intestinal damage models induced by ischemia-reperfusion, indomethacin, lipopolysaccharide-associated sepsis, trinitrobenzene sulfonic acid, and dextran sulfate sodium, indicating that activation of HO-1 may act as an endogenous defensive mechanism to reduce inflammation and tissue injury in the gastrointestinal tract. In addition, CO derived from HO-1 is shown to be involved in the regulation in gastro-intestinal motility. These in vitro and in vivo data suggest that HO-1 may be a novel therapeutic target in patients with gastrointestinal diseases.

No MeSH data available.


Related in: MedlinePlus