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[Physiological importance of calpains in gastric mucosal defense]
Shoji Hata1, Hiroyuki Sorimachi
1Calpain Project, Tokyo Metropolitan Institute of Medical Science.
Abstract:
The continuous and/or improper ingestion of irritants, including alcohol, NSAIDs, and Helicobacter pylori, often leads to serious gastropathies, affecting a wide range of people. A complex gastric defense system works to protect against these threats, for example by secreting mucus. Recently, by analysis of gene targeting mice for two gastrointestinal-tract-specific calpains, calpain-8 and calpain-9, we have demonstrated that they are cooperatively involved in the mucosal defense against stress-induced gastropathies. Calpains-8 and -9 are members of Ca2+ -dependent intracellular proteases comprising a superfamily in almost all eukaryotes, and form a functional complex, "G-calpain", expressed specifically in the mucus-producing cells. In this review, we show our recent results on calpains -8 and -9, and discuss gastric mucosal defense mechanisms involving them.
Insights
Gastric irritants like alcohol and NSAIDs cause gastropathies. Calpain-8 and calpain-9 form a complex that protects the gastric mucosa against these damaging agents.
Area of Science:
- Biochemistry
- Molecular Biology
- Gastroenterology
Context:
- Gastric mucosal integrity is crucial for preventing gastropathies caused by irritants such as alcohol, NSAIDs, and Helicobacter pylori.
- The stomach possesses a complex defense system, including mucus secretion, to counteract these damaging agents.
- Understanding the molecular mechanisms of gastric defense is essential for developing therapeutic strategies.
Purpose:
- To review recent findings on the roles of calpain-8 and calpain-9 in gastric mucosal defense.
- To elucidate the cooperative function of calpain-8 and calpain-9 in protecting the stomach against stress-induced gastropathies.
- To discuss the involvement of these proteases in the overall gastric mucosal defense mechanisms.
Summary:
- Calpain-8 and calpain-9 are Ca2+-dependent intracellular proteases that form a functional complex known as "G-calpain".
- This G-calpain complex is specifically expressed in mucus-producing cells of the gastric mucosa.
- Gene targeting studies in mice demonstrate that calpain-8 and calpain-9 cooperatively defend the gastric mucosa against stress-induced gastropathies.
Impact:
- The findings highlight the critical role of G-calpain in maintaining gastric mucosal defense.
- This research provides insights into novel molecular targets for treating gastropathies.
- Understanding the function of calpains in the stomach may lead to new therapeutic interventions for gastrointestinal disorders.
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