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Mitochondrial disorders in NSAIDs-induced small bowel injury.

Watanabe T, Tanigawa T, Nadatani Y, Otani K, Machida H, Okazaki H, Yamagami H, Watanabe K, Tominaga K, Fujiwara Y, Arakawa T - J Clin Biochem Nutr (2011)

Bottom Line: Many non-steroidal anti-inflammatory drugs directly cause mitochondrial disorders, which are attributable to uncoupling of oxidative phosphorylation induced by opening of the mega channel called mitochondrial permeability transition pore on the mitochondrial membrane by non-steroidal anti-inflammatory drugs.Bile acids and tumor necrosis factor-α also can open the permeability transition pore.The permeability transition pore opening induces the release of cytochrome c from mitochondrial matrix into the cytosol, which triggers a cascade of events that will lead to cell death.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.

ABSTRACT
Recent studies using small bowel endoscopy revealed that non-steroidal anti-inflammatory drugs including low-dose aspirin, can often induce small bowel injury. Non-steroidal anti-inflammatory drugs-induced small bowel mucosal injury involves various factors such as enterobacteria, cytokines, and bile. Experimental studies demonstrate that both mitochondrial disorders and inhibition of cyclooxygenases are required for development of non-steroidal anti-inflammatory drugs-induced small bowel injury. Mitochondrion is an organelle playing a central role in energy production in organisms. Many non-steroidal anti-inflammatory drugs directly cause mitochondrial disorders, which are attributable to uncoupling of oxidative phosphorylation induced by opening of the mega channel called mitochondrial permeability transition pore on the mitochondrial membrane by non-steroidal anti-inflammatory drugs. Bile acids and tumor necrosis factor-α also can open the permeability transition pore. The permeability transition pore opening induces the release of cytochrome c from mitochondrial matrix into the cytosol, which triggers a cascade of events that will lead to cell death. Therefore these mitochondrial disorders may cause disturbance of the mucosal barrier function and elevation of the small bowel permeability, and play particularly important roles in early processes of non-steroidal anti-inflammatory drugs-induced small bowel injury. Although no valid means of preventing or treating non-steroidal anti-inflammatory drugs-induced small bowel injury has been established, advances in mitochondrial studies may bring about innovation in the prevention and treatment of this kind of injury.

No MeSH data available.


Related in: MedlinePlus

Structure and function of mitochondrial permeability transition pore. HK, hexokinase; BR, benzodiazepine receptor; CK, creatinekinase; ANT, adenine nucleotide translocase; VDAC, voltage-dependent anion channel; CypD, cyclophilin D, OM, outer membrane; IM, inner membrane.
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Figure 2: Structure and function of mitochondrial permeability transition pore. HK, hexokinase; BR, benzodiazepine receptor; CK, creatinekinase; ANT, adenine nucleotide translocase; VDAC, voltage-dependent anion channel; CypD, cyclophilin D, OM, outer membrane; IM, inner membrane.

Mentions: Mitochondrial permeability transition (elevation of permeability across the mitochondrial membrane) is a phenomenon of sharp elevation in the permeability of substances (below 1,500 Da in molecular weight) across the mitochondrial membrane.(24) This phenomenon is initiated by opening of the mega-channel called mitochondrial permeability transition pore (PTP; composed of voltage-dependent anion channel (porin), adenine nucleotide translocase, cyclophilin D, etc.) on the mitochondrial membrane (Fig. 2). When the PTP is opened, low-molecularweight substrates can freely penetrate the mitochondrial matrix, carrying along with them water and resulting in mitochondrial swelling and the release of cytochrome c into the cytosol. Cytochrome c release triggers a cascade of events that will lead to either apoptosis (in ATP-replete cells) or necrosis (in ATPdepleted cells).(25–27)


Mitochondrial disorders in NSAIDs-induced small bowel injury.

Watanabe T, Tanigawa T, Nadatani Y, Otani K, Machida H, Okazaki H, Yamagami H, Watanabe K, Tominaga K, Fujiwara Y, Arakawa T - J Clin Biochem Nutr (2011)

Structure and function of mitochondrial permeability transition pore. HK, hexokinase; BR, benzodiazepine receptor; CK, creatinekinase; ANT, adenine nucleotide translocase; VDAC, voltage-dependent anion channel; CypD, cyclophilin D, OM, outer membrane; IM, inner membrane.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3045683&req=5

Figure 2: Structure and function of mitochondrial permeability transition pore. HK, hexokinase; BR, benzodiazepine receptor; CK, creatinekinase; ANT, adenine nucleotide translocase; VDAC, voltage-dependent anion channel; CypD, cyclophilin D, OM, outer membrane; IM, inner membrane.
Mentions: Mitochondrial permeability transition (elevation of permeability across the mitochondrial membrane) is a phenomenon of sharp elevation in the permeability of substances (below 1,500 Da in molecular weight) across the mitochondrial membrane.(24) This phenomenon is initiated by opening of the mega-channel called mitochondrial permeability transition pore (PTP; composed of voltage-dependent anion channel (porin), adenine nucleotide translocase, cyclophilin D, etc.) on the mitochondrial membrane (Fig. 2). When the PTP is opened, low-molecularweight substrates can freely penetrate the mitochondrial matrix, carrying along with them water and resulting in mitochondrial swelling and the release of cytochrome c into the cytosol. Cytochrome c release triggers a cascade of events that will lead to either apoptosis (in ATP-replete cells) or necrosis (in ATPdepleted cells).(25–27)

Bottom Line: Many non-steroidal anti-inflammatory drugs directly cause mitochondrial disorders, which are attributable to uncoupling of oxidative phosphorylation induced by opening of the mega channel called mitochondrial permeability transition pore on the mitochondrial membrane by non-steroidal anti-inflammatory drugs.Bile acids and tumor necrosis factor-α also can open the permeability transition pore.The permeability transition pore opening induces the release of cytochrome c from mitochondrial matrix into the cytosol, which triggers a cascade of events that will lead to cell death.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.

ABSTRACT
Recent studies using small bowel endoscopy revealed that non-steroidal anti-inflammatory drugs including low-dose aspirin, can often induce small bowel injury. Non-steroidal anti-inflammatory drugs-induced small bowel mucosal injury involves various factors such as enterobacteria, cytokines, and bile. Experimental studies demonstrate that both mitochondrial disorders and inhibition of cyclooxygenases are required for development of non-steroidal anti-inflammatory drugs-induced small bowel injury. Mitochondrion is an organelle playing a central role in energy production in organisms. Many non-steroidal anti-inflammatory drugs directly cause mitochondrial disorders, which are attributable to uncoupling of oxidative phosphorylation induced by opening of the mega channel called mitochondrial permeability transition pore on the mitochondrial membrane by non-steroidal anti-inflammatory drugs. Bile acids and tumor necrosis factor-α also can open the permeability transition pore. The permeability transition pore opening induces the release of cytochrome c from mitochondrial matrix into the cytosol, which triggers a cascade of events that will lead to cell death. Therefore these mitochondrial disorders may cause disturbance of the mucosal barrier function and elevation of the small bowel permeability, and play particularly important roles in early processes of non-steroidal anti-inflammatory drugs-induced small bowel injury. Although no valid means of preventing or treating non-steroidal anti-inflammatory drugs-induced small bowel injury has been established, advances in mitochondrial studies may bring about innovation in the prevention and treatment of this kind of injury.

No MeSH data available.


Related in: MedlinePlus