Glutathione, Stress Responses, and Redox Signaling in Lung Inflammation

Abstract

Changes in the ratio of intracellular reduced and disulfide forms of glutathione (GSH/GSSG) can affect signaling pathways that participate in various physiological responses from cell proliferation to gene expression and apoptosis. It is also now known that many proteins have a highly conserved cysteine (sulfhydryl) sequence in their active/regulatory sites, which are primary targets of oxidative modifications and thus important components of redox signaling. However, the mechanism by which oxidants and GSH/protein-cysteine-thiols actually participate in redox signaling still remains to be elucidated. Initial studies involving the role of cysteine in various proteins have revealed that cysteine-SH may mediate redox signaling via reversible or irreversible oxidative modification to Cys-sulfenate or Cys-sulfinate and Cys-sulfonate species, respectively. Oxidative stress possibly via the modification of cysteine residues activates multiple stress kinase pathways and transcription factors nuclear factor-kappaB and activator protein-1, which differentially regulate the genes for proinflammatory cytokines as well as the protective antioxidant genes. Understanding the redox signaling mechanisms for differential gene regulation may allow for the development of novel pharmacological approaches that preferentially up-regulate key antioxidants genes, which, in turn, reduce or resolve inflammation and injury. This forum article features the current knowledge on the role of GSH in redox signaling, particularly the regulation of transcription factors and downstream signaling in lung inflammation.

Camel’s Milk Protects Against Cadmium Chloride-Induced Hypocromic Microcytic Anemia and Oxidative Stress in Red Blood Cells of White Albino Rats

“…It was suggested that the decrease in cellular glutathione content due to cadmium toxicity can affect the physiological responses of cells [33] . Oxidative stress develops when the levels of antioxidants as glutathione are lowered and the production of Reactive Oxygen Species (ROS) exceeds the capacity of the cell to dispose of them [34] .…”

“…It has been reported that camel's milk contain high levels of Vitamins C, A, B2 and E and very rich in magnesium and Zinc [33] . These vitamins are antioxidants found to be useful in reducing the oxidative stress caused by toxic agent.…”

“…Another interpretation for the improvement of the parameters of the present investigation may be due to the decrease of cadmium accumulation in liver and kidneys which are important haematopoietic organs in the rats receiving Camel's milks in addition to cadmium. Camel's milk is rich in Zinc (Zn) [33] . Zinc is a trace element essential for living organisms.…”

Glutathione-Redox Balance Regulates c-rel–Driven IL-12 Production in Macrophages: Possible Implications in Antituberculosis Immunotherapy

“…The intracellular redox environment is mainly controlled by the glutathione-redox, which is defined as the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) (1) and plays critical roles in maintaining cellular homeostasis and various physiological functions (2). The cellular glutathione-redox dynamically regulates protein functions by reversible disulfide bond formation on variety of proteins, including phosphatases, kinases, and transcription factors (3)(4)(5) and is known to protect against oxidative stress (6,7). The glutathione-redox balance in macrophages is shown to be critical for mounting innate immune responses and has also been implicated in many of the pathological conditions (2,(8)(9)(10), indicating its possible potential use as a therapeutic agent.…”

Postprandial oxidative stress is modulated by dietary fat in adipose tissue from elderly people

“…$ p<0.05 versus 2-h after meal intake. Different letters: the differences between diets are statistically significant (p<0.05) (Faraci and Didion 2004;Mates et al 1999;Rahman et al 2005). Our results showed that the gene expression of the mitochondrial SOD isoform, SOD2, seems to be modulated by dietary fat rather than by the cytoplasmatic isoform SOD1.…”