Betaine modulates age-related NF-kappaB by thiol-enhancing action.
Depletion of glutathione levels and perturbations in redox status are considered to play a crucial role in aging and chronic inflammatory processes through the activation of redox sensitive transcription factors, including nuclear factor-kappaB (NF-kappaB). In the current study, we assessed the regulatory action of dietary betaine in the suppression of NF-kappaB by comparing kidney tissue from old, betaine-supplemented rats or non-betaine-supplemented rats (age 21 months) and 7 month-old rats. In addition, cultured HEK 293T cells were utilized for the molecular assessment of betaine's restorative ability of redox status when treating cells with potent glutathione (GSH)-depleting agents. Results showed that in old rats a short-term feeding (10 d) with betaine attenuated the age-related decrease in thiol levels, increase in reactive species and TNFalpha expression via NF-kappaB activation, compared to the young controls. These findings were verified in the cell-cultured system. Further investigations found that redox imbalance due to thiol depletion caused increased NF-kappaB activation, and cyclooxygenase (COX)-2 and TNFalpha levels, both of which were suppressed by betaine treatment. Based on both in vivo and in vitro data, we concluded that betaine exerts its efficacy by maintaining thiol status in the regulation of COX-2 and TNFalpha via NF-kappaB activation during aging.
Go
Eun Kyung
EK
Department of Pharmacy, College of Pharmacy, Pusan National University, Gumjung-ku, Busan 609-735, Korea.
Jung
Kyung Jin
KJ
Kim
Ji Min
JM
Lim
Hyunae
H
Lim
Hyeang Kwan
HK
Yu
Byung Pal
BP
Chung
Hae Young
HY
D000375:Aging / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001622:Betaine / Q000494:pharmacology*; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D004032:Diet; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000096:biosynthesis*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism
D000975:Antioxidants; D016328:NF-kappa B; D013438:Sulfhydryl Compounds; D014409:Tumor Necrosis Factor-alpha; D001622:Betaine; D051546:Cyclooxygenase 2; D005978:Glutathione