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Augmentation of superoxide generation in phagocytosing murine peritoneal macrophages by dietary restriction
K Hishinuma1, A Hosono, S Mashiko
1Biophoton Project, Research Development Corporation of Japan, Miyagi.
Abstract:
The effects of dietary restriction on the generation of superoxide anion (O2-) in phagocytosing mouse peritoneal macrophages (MPs) were investigated. MPs obtained from diet-restricted mice generated larger amount of O2- during phagocytosis of opsonized zymosan than those from unrestricted mice. This augmentation of the O2- generation was not inhibited by the protein kinase C (PKC) inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7). However, the augmentation was clearly disappeared when the calmodulin (CaM) antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) was added. These results strongly suggest that the augmentation of O2- generation in phagocytosing MPs by dietary restriction is due to the increased activity of CaM in the MPs, and that PKC is not involved in the augmentation. It is thought that one of the major factors for the reduced incidence of tumor and infection in diet-restricted animals is the augmentation of O2- generation in MPs.
Insights
Dietary restriction enhances superoxide anion (O2-) generation in mouse macrophages during phagocytosis. This effect is mediated by calmodulin (CaM), not protein kinase C (PKC), potentially explaining reduced tumor and infection rates in restricted animals.
Area of Science:
- Immunology
- Cell Biology
- Nutritional Science
Background:
- Dietary restriction is known to reduce the incidence of age-related diseases like cancer and infections.
- Macrophages play a crucial role in the immune response, particularly in combating pathogens and eliminating abnormal cells.
- Superoxide anion (O2-) generation is a key component of the oxidative burst in phagocytic cells.
Purpose of the Study:
- To investigate the impact of dietary restriction on superoxide anion (O2-) production in mouse peritoneal macrophages (MPs).
- To elucidate the molecular mechanisms underlying changes in O2- generation by MPs from diet-restricted mice.
Main Methods:
- Isolation of mouse peritoneal macrophages (MPs) from diet-restricted and unrestricted mice.
- Measurement of O2- generation during phagocytosis of opsonized zymosan.
- Assessment of the involvement of protein kinase C (PKC) and calmodulin (CaM) using specific inhibitors (H-7 and W-7, respectively).
Main Results:
- MPs from diet-restricted mice exhibited augmented O2- generation compared to controls.
- The enhanced O2- production was not affected by the PKC inhibitor H-7.
- The CaM antagonist W-7 completely abolished the augmentation of O2- generation.
Conclusions:
- Dietary restriction increases O2- generation in phagocytosing MPs.
- The augmentation is dependent on calmodulin (CaM) activity, suggesting its increased role.
- Protein kinase C (PKC) is not involved in this dietary restriction-induced enhancement of O2- production.
- Enhanced macrophage O2- generation may contribute to the protective effects of dietary restriction against tumors and infections.