Track topics on Twitter Track topics that are important to you
Microsomal glutathione transferase 1 (MGST1) possesses glutathione transferase and peroxidase activities and is active in biotransformation of xenobiotics and in defense against oxidative stress. To assess MGST1 role in the development and functioning of PC12 cells, we constructed a cell line with reduced MGST1 (PC12_M). Real-time PCR and immunoblot assays showed MGST1 expression lowered to 60 % and immunocytochemical analyses demonstrated an altered concentration and distribution of the enzyme. PC12_M cells revealed a larger tendency to grow in clusters, weaker adhesion, irregular shape of bodies, short neurite outgrowth and higher percentage of necrotic cells (34 %). The total GSTs activity determined with non-specific substrate CDNB (1-chloro-2,4-dinitrobenzene) decreased by 15-20 %, whereas that with DCNB (2,4-dichloro-1-nitrobenzene), a substrate more specific for cytosolic GSTs, was similar to the one in control cells. This suggests that reduction of MGST1 cannot be compensated by other glutathione transferases. In PC12_M cells the total glutathione content was higher by 15-20 %, whereas the GSSG/GSH ratio was lower than in control cells. Moreover, the laminin-dependent migration rate was much faster in control cells than in PC12_M, suggesting some alterations in the metastatic potential of the line with suppressed MGST1. The amount of MAP kinases (p38, JNK, ERK1/2) was elevated in PC12_M cells but their phosphorylation level declined. Microarray analysis showed changed expression of several genes, which may be linked with differentiation and necrosis of PC12_M cells. Our data suggest that MGST1 could be an important regulator of PC12 cells development and might have significant effects on cell growth and proliferation, probably through altered expression of genes with different biological function.
Department of Molecular Neurochemistry, Medical University, Łódź, Poland.
This article was published in the following journal.
Name: Acta biochimica Polonica
SIRT2 plays important roles in multiple biological processes. It is unclear whether SIRT2 affects antioxidant capacity by modulating Nrf2, a key transcription factor for multiple antioxidant genes. By...
Oxidative stress is involved in the pathogenesis of several neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Natural products are considered as therapeutically useful antioxida...
Oxidative stress is closely related to the pathogenesis of neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. However, the underlying antioxidant mechanisms of ferulic ac...
Neurodegenerative disorders are chronic and progressive disease. Exendin-4 (Ex-4) can function as a neuroprotective agent and has novel therapeutic ability for the treatment of neurodegenerative disor...
The immune status, components of the glutathione redox system, the activity of antioxidant enzymes and metabolism of purine nucleotides have been investigated in animals with experimental hypothyroidi...
This study is for the patient with breast cancer. To take part in this study, external beam radiation therapy needs to be part of the treatment plan. Reduced glutathione, an ingredient of ...
This is a double-blind, placebo-controlled crossover study to evaluate the safety and efficacy of glutathione alone or glutathione, vitamin C and NAC treatment in children with autism who ...
The glutathione synthetase deficiency, inborn error of metabolism of autosomal recessive inheritance, is a rare disease (70 patients described in the world). The outcome of these patients ...
RATIONALE: Oxidized glutathione (NOV-002) may stimulate the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as doxorubicin, cyclophospha...
The aim of the study is to determine mechanisms leading to glutathione deficiency in low birth weight newborn babies. Compared to full term neonates, depletion in this population may be d...
A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.
Catalyzes the oxidation of GLUTATHIONE to GLUTATHIONE DISULFIDE in the presence of NADP+. Deficiency in the enzyme is associated with HEMOLYTIC ANEMIA. Formerly listed as EC 188.8.131.52.
An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 184.108.40.206.
A glutathione transferase that catalyzes the conjugation of electrophilic substrates to GLUTATHIONE. This enzyme has been shown to provide cellular protection against redox-mediated damage by FREE RADICALS.
A single SELENOCYSTEINE containing protein that binds reduced GLUTATHIONE and can act as an antioxidant.
Stress is caused by your perception of situations around you and then the reaction of your body to them. The automatic stress response to unexpected events is known as 'fight or flight'. Discovered by Walter Cannon in 1932, it is the release of h...
Enzymes are proteins that catalyze (i.e., increase the rates of) chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical re...