Betaine Modulates Age-Related NF-.KAPPA.B by Thiol-Enhancing Action

Abstract

Oxidative stress is a condition where the reduction and oxidation (redox) balance between reactive species (RS) such as superoxide anion ( · O 2 Ϫ ), hydrogen peroxide (H 2 O 2 ), peroxynitrite (ONOO Ϫ ), and hydroxyl radical ( · OH) and antioxidant species such as glutathione (GSH) and thioredoxin (Trx) is disrupted. 1-3)Oxidant-related reactions and cellular redox imbalance are implicated in a number of human diseases and aging. 4,5) Further, biological systems are protected against oxidative stress by a diversity of mechanisms designed to suppress the pernicious oxidative pathway. Numerous antioxidants are known to forestall oxidative damage or to limit its propagation. GSH, is a most abundant and an important intracellular thiol redox regulator that plays a major role in both the maintenance of redox status and in the protection of cells from electrophilic and oxidative attacks. 6) Many researchers who are interested in studying changes in the redox status rely on GSH levels as a reliable indicator of an organism's redox status. GSH depletion causes various biochemical and pathological changes, including mitochondrial dysfunction and swelling. 7,8) GSH depletion also is linked to aging processes, cardiovascular and neurodegenerative diseases. [9][10][11] A gradual rise of oxidative stress due to disrupted redox regulation during aging can influence the gene transcription and signal transduction pathways. The gene response to oxidative stress is seen due to the redox-sensitive transcription factors that modulate gene regulation. NF-kB is among the most important transcription factors shown to be exquisitely sensitive to oxidative stress conditions. 12) NF-kB regulates the activity of many genes, such as cyclooxygenase-2 (COX-2), TNFa, inducible NO synthase, and adhesion molecules. 13,14) Most of genes activated by NF-kB transcription factor are shown to be pro-inflammatory and involved in inflammation processes. In aged organisms, inflammatory reactions lead to a chronic pro-inflammatory state as evidenced from the activation of pro-inflammatory gene expression. 15,16) Betaine was first discovered in the juice of sugar beets (Beta vulgaris) in the 19th century and now found widely in various microorganisms, plant, and animals. 17) In Southeast Asia, this water-soluble component of Lycium chinensis has been used in traditional oriental medicine for the treatment of hepatic disorders.18) The biological function of betaine is proposed to act as an osmolyte to protect cells under stress 19) as a catabolic source of methyl through transmethylation in many biochemical pathways.17) As a methyl donor, betaine participates in methionine metabolism by its ability to convert homocysteine (Hcy) to methionine. 17,20) Recently, our lab published a paper on betaine's ability to suppress NF-kB during aging.15) However, this paper did not fully address how betaine exerts its regulatory role in the suppression of NF-kB.In the present study, we attempt to document that betaine decreases NF-kB through modulation of the cellular ...

Studies on the protective effects of betaine against oxidative damage during experimentally induced restraint stress in Wistar albino rats

“…7,8,9,10 and 11). It probably did so by its antioxidant action (Go et al 2007) against restraint stress-induced lipid peroxidation. Previous studies by Erman et al (2004) indicated that lipotropes inhibit lipid peroxidation in cellular membranes as a result of distinct biophysical interactions with membrane lipid bilayer.…”

Betaine prevents homocysteine-induced memory impairment via matrix metalloproteinase-9 in the frontal cortex

“…Dietary betaine suppresses the activation of nuclear factor-B (NF-B) that is induced by oxidative stress and also suppresses protein expressions of proinflammatory molecules, such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and tumor necrosis factor (TNF)-␣, in aged rat kidneys [19,20]. However, the effects of betaine on central nervous system function in animals are poorly understood.…”

Protective Effect of Betaine on Changes in the Levels of Membrane-bound ATPase activity and Mineral Status in Experimentally Induced Myocardial Infarction in Wistar Rats

“…It has been shown that betaine has the ability to enhance thiol levels as an antioxidative defense system. Go et al [53] reported that betaine exerts its efficacy (both in vivo and in vitro) by maintaining thiol status in the regulation of COX-2 and TNFalpha via NF-kappaB activation during aging in rats. There is also evidence that administration of betaine along with ethanol restored glutathione and tissue thiols in rats [54].…”