Modulation of intracellular glutathione affects adipogenesis in 3T3‐L1 cells

Vigilanza, Paola; Aquilano, Katia; Baldelli, Sara; Rotilio, Giuseppe; Ciriolo, Maria Rosa

doi:10.1002/jcp.22542

Cited by 69 publications

(65 citation statements)

References 57 publications

(67 reference statements)

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“…PGC-1a and p53 siRNA oligonucleotides are reported in Table 1. ROS/RNS levels were assayed by means of DCF-DA staining as previously reported (44).…”

Section: Cell Cultures Transfections and Ros/rns Assaymentioning

confidence: 99%

p53 Orchestrates the PGC-1α-Mediated Antioxidant Response Upon Mild Redox and Metabolic Imbalance

Aquilano

Baldelli²,

Pagliei

et al. 2013

Antioxidants & Redox Signaling

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173

183

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Aims: The transcriptional coactivator peroxisome proliferator-activated receptor-c coactivator-1 a (PPARGC1A or PGC-1a) is a powerful controller of cell metabolism and assures the balance between the production and the scavenging of pro-oxidant molecules by coordinating mitochondrial biogenesis and the expression of antioxidants. However, even though a huge amount of data referring to the role of PGC-1a is available, the molecular mechanisms of its regulation at the transcriptional level are not completely understood. In the present report, we aim at characterizing whether the decrease of antioxidant glutathione (GSH) modulates PGC-1a expression and its downstream metabolic pathways. Results: We found that upon GSH shortage, induced either by its chemical depletion or by metabolic stress (i.e., fasting), p53 binds to the PPARGC1A promoter of both human and mouse genes, and this event is positively related to increased PGC-1a expression. This effect was abrogated by inhibiting nitric oxide (NO) synthase or guanylate cyclase, implicating NO/cGMP signaling in such a process. We show that p53-mediated PGC-1a upregulation is directed to potentiate the antioxidant defense through nuclear factor (erythroid-derived 2)-like2 (NFE2L2)-mediated expression of manganese superoxide dismutase (SOD2) and c-glutamylcysteine ligase without modulating mitochondrial biogenesis. Innovation and Conclusions: We outlined a new NO-dependent signaling axis responsible for survival antioxidant response upon mild metabolic stress (fasting) and/or oxidative imbalance (GSH depletion). Such signaling axis could become the cornerstone for new pharmacological or dietary approaches for improving antioxidant response during ageing and human pathologies associated with oxidative stress. Antioxid. Redox Signal. 18, 386-399.

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“…PGC-1a and p53 siRNA oligonucleotides are reported in Table 1. ROS/RNS levels were assayed by means of DCF-DA staining as previously reported (44).…”

Section: Cell Cultures Transfections and Ros/rns Assaymentioning

confidence: 99%

p53 Orchestrates the PGC-1α-Mediated Antioxidant Response Upon Mild Redox and Metabolic Imbalance

Aquilano

Baldelli²,

Pagliei

et al. 2013

Antioxidants & Redox Signaling

Self Cite

173

183

View full text Add to dashboard Cite

show abstract

“…These pathways and regulators include glutathione (Vigilanza et al, 2010), the Janus kinase-signal transducer and activator of transcription 3 (JAK-STAT3) pathway (Zhang et al, 2011), SMAD signalling (Marchildon et al, 2010;Tan et al, 2011), ribosomal protein S6 kinase 1 (S6K1) (Carnevalli et al, 2010) and components of the insulin signalling cascade, such as AKT ) and a newly discovered regulator of this pathway, inositol pyrophosphate (Chakraborty et al, 2010). New transcriptional regulators of stem cell fate that are controlled by these pathways also continue to be identified.…”

Section: Signals To Differentiatementioning

confidence: 99%

Adipogenesis at a glance

Lowe

O’Rahilly

Rochford

2011

Journal of Cell Science

305

206

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“…(33). Another independent study showed that ROS facilitate adipocyte differentiation in 3T3-L1 cells again by accelerating the MCE phase and activating C/EBPβ, whereas exposure to broadly-acting antioxidants such as N-acetyl cysteine greatly inhibited adipogenesis (9).…”

Section: Discussionmentioning

confidence: 99%

Nrf2 activation diminishes during adipocyte differentiation of ST2 cells

Habeos¹

2011

Int J Mol Med

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Abstract. Adipocyte differentiation (adipogenesis) is a highly controlled process known to be affected, among other factors, by the redox status of the cell. Nrf2 (NFE2-related factor 2) is a transcription factor that orchestrates the expression of a battery of antioxidant and detoxification genes under both basal and stress conditions. The present study investigated the activation of Nrf2 during adipocyte differentiation using as a model the mouse bone marrow-derived ST2 cell line. Treatment of ST2 cells with a differentiation cocktail containing IBMX, indomethacin, hydrocortisone and insulin induced differentiation into adipocytes over 5 days. During adipogenesis, the intracellular glutathione redox potential, which is an indicator of oxidative stress levels, became steadily more oxidized, as shown by real-time measurement in differentiating ST2 cells stably transfected with a redox-sensitive Grx1-roGFP2 fusion protein.The nuclear abundance of Nrf2 was assessed by Western immunoblotting and its DNA binding activity by EMSA (electrophoretic mobility shift assay) performed on nuclear protein extracts prepared every 24 h. The nuclear abundance of Nrf2 continuously decreased during adipogenesis in ST2 cells. Its DNA binding activity reached a nadir during the first two days of differentiation, after which it increased slightly without approaching its initial level. The pattern of Nrf2 DNA binding corresponded to its transcriptional activity as assessed in ST2 cells stably transfected with a reporter construct bearing a Nrf2 bind site upstream of the luciferase gene. In conclusion, the activation of Nrf2 decreased significantly during adipogenesis. The observed changes might lead to increased oxidative stress levels that could facilitate the differentiation process. These findings could shed new light on the pathogenesis of obesity, in which the adipose tissue and oxidative stress play prominent roles.

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Modulation of intracellular glutathione affects adipogenesis in 3T3‐L1 cells

Cited by 69 publications

References 57 publications

p53 Orchestrates the PGC-1α-Mediated Antioxidant Response Upon Mild Redox and Metabolic Imbalance

p53 Orchestrates the PGC-1α-Mediated Antioxidant Response Upon Mild Redox and Metabolic Imbalance

Adipogenesis at a glance

Nrf2 activation diminishes during adipocyte differentiation of ST2 cells

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