Activation of stress signaling pathways by electrophilic oxidized and nitrated lipids

Kansanen, Emilia; Jyrkkänen, Henna‐Kaisa; Levonen, Anna–Liisa

doi:10.1016/j.freeradbiomed.2011.11.038

Cited by 194 publications

(131 citation statements)

References 99 publications

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“…Also, other members of the ATF family, ATF2 and -3, were predicted to be activated in response to 15d-PGJ 2 preferentially in the GR SUMOylation-competent cells. ATF4 and ATF3 are transcription factors integral to the unfolded protein response caused by endoplasmic reticulum stress (38,39). ATF4 is also involved in cellular antioxidant protection (40), and its expression has been shown to be repressed by glucocorticoids (41).…”

Section: Discussionmentioning

confidence: 99%

Electrophilic Lipid Mediator 15-Deoxy-Δ^12,14-Prostaglandin J₂ Modifies Glucocorticoid Signaling via Receptor SUMOylation

Paakinaho

Kaikkonen

Levonen

2014

Molecular and Cellular Biology

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c Cortisol, the central stress hormone in humans, activates the glucocorticoid receptor (GR). Anti-inflammatory effects are the most important pharmaceutical effects mediated by the GR. Inasmuch as electrophilic cyclopentenone prostaglandin 15-deoxy-⌬ 12,14 -prostaglandin J 2 (15d-PGJ 2 ) has potent anti-inflammatory properties and activates the SUMOylation pathway, we have investigated the effect of 15d-PGJ 2 on glucocorticoid signaling and receptor SUMOylation. To this end, we studied isogenic HEK293 cells expressing either wild-type GR or SUMOylation-defective GR. Interestingly, 15d-PGJ 2 triggered SUMO-2 and -3 (SUMO-2/3) modification in the primary SUMOylation sites of the GR. Gene expression profiling and pathway analyses indicate that 15d-PGJ 2 inhibits GR signaling in a genome-wide fashion that is significantly dependent on the GR SUMOylation sites. Chromatin immunoprecipitation assays showed that the repressive effect of 15d-PGJ 2 on GR target gene expression occurs in parallel with the inhibition of receptor binding to the target gene chromatin. Furthermore, depletion of UBC9, the sole SUMO E2 conjugase, from HEK293 cells confirmed the involvement of active SUMOylation in the regulatory process. Taken together, our data indicate that GR SUMOylation modulates the glucocorticoid signaling during acute cell stress. Our data also suggest that GR SUMOylation modulates cross talk of the glucocorticoid signaling with other transcription factors that are responsive to cell stress.

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Section: Discussionmentioning

confidence: 99%

Electrophilic Lipid Mediator 15-Deoxy-Δ^12,14-Prostaglandin J₂ Modifies Glucocorticoid Signaling via Receptor SUMOylation

Paakinaho

Kaikkonen

Levonen

2014

Molecular and Cellular Biology

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“…Bold mediators indicate those studied in the present study and our previous work . Defences during estivation and arousal Keap1-Nrf2 pathway, the heat shock response pathway and the unfolded protein response pathway (Kansanen et al, 2012). The Keap1-Nrf2 pathway regulates the expression of genes that corresponds to the 'antioxidant responsive elements' (ARE).…”

Section: Adaptive Strategies To Withstand Hypometabolic Situationsmentioning

confidence: 99%

“…This pathway shows some overlap to the Nrf2-signaling pathway because inducers of endoplasmic reticulum stress activate Nrf2 via induced phosphorylation (Cullinan et al, 2003). Also, these protective pathways show a cross-talk at the level of signaling proteins (Kansanen et al, 2012).…”

Section: Adaptive Strategies To Withstand Hypometabolic Situationsmentioning

confidence: 99%

Antioxidant and molecular chaperone defenses during estivation and arousal in the South American apple-snailPomacea canaliculata

Giraud-Billoud

Vega

Tosi

et al. 2012

Journal of Experimental Biology

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SUMMARYThe invasive Pomacea canaliculata estivates during periods of drought and should cope with harmful effects of reoxygenation during arousal. We studied thiobarbituric acid reactive substances (TBARS), enzymatic (superoxide dismutase, SOD and catalase, CAT) and non-enzymatic antioxidants (uric acid and reduced glutathione), and heat shock protein expression (Hsc70, Hsp70 and Hsp90) in (1) active control snails, (2) snails after 45days of estivation, and (3) aroused snails 20min and (4) 24h after water exposure, in midgut gland, kidney and foot. Both kidney and foot (but not the midgut gland) showed a TBARS increase during estivation and a decrease after arousal. Tissue SOD and CAT did not change in any experimental groups. Uric acid increased during estivation in all tissues, and it decreased after arousal in the kidney. Allantoin, the oxidation product of uric acid, remained constant in the midgut gland but it decreased in the kidney until 20min after arousal; however, allantoin levels rose in both kidney and foot 24h after arousal. Reduced glutathione decreased during estivation and arousal, in both midgut gland and kidney, and it remained constant in the foot. Hsc70 and Hsp70 kidney levels were stable during the activity-estivation cycle and Hsp90 expression decreases during estivation and recovers in the early arousal. In foot, the expression of Hsp70 and Hsp90 was high during activity and estivation periods and disminished after arousal. Results indicate that a panoply of antioxidant and molecular chaperone defences may be involved during the activity-estivation cycle in this freshwater gastropod.

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“…It is shown that under normal redox status, Nrf2 is mostly bound to a cytosolic protein Keap 1 and, thus, plays a minor role in gene regulation. 21,22,35 However, stimulatory factors that include oxidants or antioxidants, such as sulforaphane, can dissociate the Nrf2-Keap 1 complex. 21,22,35 The stimulated Nrf2 migrates/translocates to nucleus and activates a battery of phase II antioxidant enzymes, such as NQO1, GST, and HO-1, which in turn help to normalize the redox status of the cell.…”

Section: Discussionmentioning

confidence: 99%

“…21,22,35 However, stimulatory factors that include oxidants or antioxidants, such as sulforaphane, can dissociate the Nrf2-Keap 1 complex. 21,22,35 The stimulated Nrf2 migrates/translocates to nucleus and activates a battery of phase II antioxidant enzymes, such as NQO1, GST, and HO-1, which in turn help to normalize the redox status of the cell. 21,22,35 In the present study, we found that BSO and sulforaphane caused a modest Nrf2 nuclear translocation, which was reflected by a moderate increase in the activities NQO1, GST, and HO-1.…”

Section: Discussionmentioning

confidence: 99%

Transcription Factor Nrf2 Protects Renal Dopamine D1 Receptor Function During Oxidative Stress

Banday

Lokhandwala

2013

Hypertension

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Abstract-The renal dopaminergic system plays a significant role in controlling sodium excretion and blood pressure (BP).Overwhelming evidence shows that oxidative stress downregulates renal dopamine receptors (D1R), and antioxidant supplementation protects D1R function. However, the mechanisms for benefits of antioxidants in protecting D1R function are unknown. We investigated the role of nuclear factor E2-related factor 2 (Nrf2), a redox-sensitive transcription factor, in reducing oxidative stress, protecting renal D1R function and lowering BP in rats. Male Sprague-Dawley rats were treated with L-buthionine-sulfoximine (BSO) and sulforaphane for 4 weeks. Rats treated with BSO exhibited significant increase in oxidative stress and BP. BSO treatment reduced renal D1R expression and abolished SKF38393 (a D1R agonist)-induced Na/K-ATPase and Na/H-exchanger (NHE3) inhibition. Also, in these rats, SKF38393 failed to promote sodium excretion. BSO caused an increase in nuclear factor-κB expression, a modest nuclear translocation of Nrf2 and a moderate activation of phase II antioxidant enzymes. Treatment of rats with sulforaphane alone induced modest activation of Nrf2 and phase II antioxidant enzymes, although having no effect on BP, redox status, or D1R function. However, sulforaphane prevented oxidative stress, protected D1R function, and abrogated hypertension in BSO-treated rats. In these animals, sulforaphane, whereas attenuating nuclear factor-κB activation, caused a robust stimulation of Nrf2 and phase II antioxidant enzyme pathway. In conclusion, oxidative stress via nuclear factor-κB activation downregulated D1R function causing a decrease in sodium excretion, which contributed to an increase in BP. Sulforaphane via activation of Nrf2-phase II antioxidant enzyme pathway mitigated oxidative stress and nuclear factor-κB activation, preserved D1R function, and prevented hypertension. (Hypertension. 2013;62:512-517.)

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Activation of stress signaling pathways by electrophilic oxidized and nitrated lipids

Cited by 194 publications

References 99 publications

Electrophilic Lipid Mediator 15-Deoxy-Δ^12,14-Prostaglandin J₂ Modifies Glucocorticoid Signaling via Receptor SUMOylation

Electrophilic Lipid Mediator 15-Deoxy-Δ^12,14-Prostaglandin J₂ Modifies Glucocorticoid Signaling via Receptor SUMOylation

Antioxidant and molecular chaperone defenses during estivation and arousal in the South American apple-snailPomacea canaliculata

Transcription Factor Nrf2 Protects Renal Dopamine D1 Receptor Function During Oxidative Stress

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Activation of stress signaling pathways by electrophilic oxidized and nitrated lipids

Cited by 194 publications

References 99 publications

Electrophilic Lipid Mediator 15-Deoxy-Δ12,14-Prostaglandin J2 Modifies Glucocorticoid Signaling via Receptor SUMOylation

Electrophilic Lipid Mediator 15-Deoxy-Δ12,14-Prostaglandin J2 Modifies Glucocorticoid Signaling via Receptor SUMOylation

Antioxidant and molecular chaperone defenses during estivation and arousal in the South American apple-snailPomacea canaliculata

Transcription Factor Nrf2 Protects Renal Dopamine D1 Receptor Function During Oxidative Stress

Contact Info

Product

Resources

About

Electrophilic Lipid Mediator 15-Deoxy-Δ^12,14-Prostaglandin J₂ Modifies Glucocorticoid Signaling via Receptor SUMOylation

Electrophilic Lipid Mediator 15-Deoxy-Δ^12,14-Prostaglandin J₂ Modifies Glucocorticoid Signaling via Receptor SUMOylation