Aging effect on myeloperoxidase in rat kidney and its modulation by calorie restriction
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Published on: July 3, 2013
Tae Gen Son1, Yani Zou, Byung Pal Yu
1Department of Pharmacy, College of Pharmacy, Aging Tissue Bank, Longevity Life Science and Technology Institutes, Pusan National University, Gumjung-gu, Busan 609-735, South Korea.
Abstract:
Myeloperoxidase (MPO), a heme protein existing in neutrophil and monocyte, is implicated in various stages of inflammatory conditions with the production of a variety of potent oxidants. To investigate the extent of the involvement of MPO in aging, we measured MPO activities in kidney of rats at different ages maintained with an ad libitum (AL) or a calorie restriction (CR) dietary regimen. Results showed that the MPO activities increased during aging in AL rats, but were significantly attenuated by CR. This result was consistent with altered protein level of MPO during aging. In addition, we were able to detect dityrosine that is a stable end MPO-oxidation product. The amount of dityrosine increased in old AL, but not in old CR rats. To examine the source responsible for increased MPO activity during aging for leukocyte recruitment and infiltration, the levels of vascular cell adhesion molecule (VCAM-1) protein were measured. The level of VCAM-1 showed age-dependent increase in AL rats, which was correlated with higher activity of MPO in old AL rats. Furthermore, we have found that LPS-induced inflammation increased the activity and protein levels of MPO, and VCAM-1 expression in young rat kidneys. These findings suggest that increased MPO activity with aging may related to increased recruitment of inflammatory cells, contributing to protein oxidation accumulation in the aging process. We propose that age-related alterations of MPO, dityrosine, and VCAM were modulated by CR through its anti-inflammatory action.
Insights
Calorie restriction (CR) reduces age-related increases in kidney myeloperoxidase (MPO) activity and MPO-oxidation products like dityrosine in rats. CR mitigates inflammation and cellular adhesion molecule VCAM-1, suggesting a role in healthy aging.
Area of Science:
- Biochemistry
- Aging Research
- Inflammation Biology
Background:
- Myeloperoxidase (MPO) is a key enzyme in neutrophil and monocyte function, producing oxidants during inflammation.
- Age-related inflammation and oxidative stress are significant factors in tissue dysfunction.
- Calorie restriction (CR) is known to modulate aging processes and inflammatory responses.
Purpose of the Study:
- To investigate the role of MPO in kidney aging.
- To determine the effect of CR on MPO activity and its oxidation products during aging.
- To explore the relationship between MPO, VCAM-1, and inflammation in aging kidneys.
Main Methods:
- Measurement of MPO activity and protein levels in rat kidneys across different ages and dietary regimens (ad libitum vs. CR).
- Quantification of dityrosine, a stable MPO oxidation product.
- Assessment of vascular cell adhesion molecule-1 (VCAM-1) protein levels.
- Induction of inflammation using lipopolysaccharide (LPS) in young rats.
Main Results:
- MPO activity and protein levels increased with age in ad libitum-fed rats but were attenuated by CR.
- Dityrosine levels increased in aged rats on an ad libitum diet, but not in CR rats.
- Age-dependent increases in VCAM-1 were observed in ad libitum rats and correlated with MPO activity.
- LPS-induced inflammation increased MPO and VCAM-1 in young rat kidneys.
Conclusions:
- Increased kidney MPO activity during aging may contribute to oxidative stress and inflammation through enhanced inflammatory cell recruitment.
- CR effectively attenuates age-related increases in MPO, dityrosine, and VCAM-1, likely via anti-inflammatory mechanisms.
- These findings highlight MPO as a potential therapeutic target for mitigating age-related kidney damage.
