Valproic Acid Influences MTNR1A Intracellular Trafficking and Signaling in a β-Arrestin 2-Dependent Manner

Li, Hong; Jiang, Quan; Long, Sen; Wang, Huan; Zhang, Ling di; Tian, Yun; Wang, Cheng kun; Cao, Jing; Tao, Rong; Huang, Jiayi; Liao, Mei; Lu, Ying; Fukunaga, Kohji; Zhou, Nai ming; Han, Feng

doi:10.1007/s12035-014-9085-y

Cited by 15 publications

(8 citation statements)

References 51 publications

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“…Interestingly, valproate has recently been shown to inhibit βARR2-mediated ERK2 activation downstream of the melatonin receptor type 1 in transfected HEK293 and Neuro2A cells (35), therefore supporting our findings in vivo.…”

Section: High-dose Chronic Valproate Treatment Elicits Inhibition Of supporting

confidence: 90%

“…Our results also indicate that valproate can interfere with at least two modalities of βARR2-mediated signaling, the negative regulation of AKT and the activation of ERK2. Interestingly, a similar effect of valproate has recently been reported in neuroblastoma cells (35). However, this effect does not seem to be apparent at all doses, as only the VAL 25 regimen resulted in a βARR2-dependent reduction of ERK activity in vivo.…”

Section: Discussionsupporting

confidence: 64%

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FXR1P is a GSK3β substrate regulating mood and emotion processing

Del’Guidice

Latapy

Rampino

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

112

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Inhibition of glycogen synthase kinase 3β (GSK3β) is a shared action believed to be involved in the regulation of behavior by psychoactive drugs such as antipsychotics and mood stabilizers. However, little is known about the identity of the substrates through which GSK3β affects behavior. We identified fragile X mental retardation-related protein 1 (FXR1P), a RNA binding protein associated to genetic risk for schizophrenia, as a substrate for GSK3β. Phosphorylation of FXR1P by GSK3β is facilitated by prior phosphorylation by ERK2 and leads to its down-regulation. In contrast, behaviorally effective chronic mood stabilizer treatments in mice inhibit GSK3β and increase FXR1P levels. In line with this, overexpression of FXR1P in the mouse prefrontal cortex also leads to comparable mood-related responses. Furthermore, functional genetic polymorphisms affecting either FXR1P or GSK3β gene expression interact to regulate emotional brain responsiveness and stability in humans. These observations uncovered a GSK3β/FXR1P signaling pathway that contributes to regulating mood and emotion processing. Regulation of FXR1P by GSK3β also provides a mechanistic framework that may explain how inhibition of GSK3β can contribute to the regulation of mood by psychoactive drugs in mental illnesses such as bipolar disorder. Moreover, this pathway could potentially be implicated in other biological functions, such as inflammation and cell proliferation, in which FXR1P and GSK3 are known to play a role.

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Section: High-dose Chronic Valproate Treatment Elicits Inhibition Of supporting

confidence: 90%

Section: Discussionsupporting

confidence: 64%

FXR1P is a GSK3β substrate regulating mood and emotion processing

Del’Guidice

Latapy

Rampino

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

112

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“…YFP‐labeled TIGAR (TIGAR‐pEYFPC1) and CFP‐labeled calmodulin (CaM‐pECFPC1) plasmids were co‐transfected into HEK‐293 cells for Fluorescence Resonance Energy Transfer (FRET) assay . Acceptor photobleaching experiments were completed using a Nikon A1 confocal microscope (FV1000‐fluoview) with a 40 mW argon laser.…”

Section: Methodsmentioning

confidence: 99%

Melatonin ameliorates hypoglycemic stress‐induced brain endothelial tight junction injury by inhibiting protein nitration of TP53‐induced glycolysis and apoptosis regulator

Wang

Ahmed

Jiang

et al. 2017

Journal of Pineal Research

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Severe hypoglycemia has a detrimental impact on the cerebrovasculature, but the molecular events that lead to the disruption of the integrity of the tight junctions remain unclear. Here, we report that the microvessel integrity was dramatically compromised (59.41% of wild‐type mice) in TP53‐induced glycolysis and apoptosis regulator (TIGAR) transgenic mice stressed by hypoglycemia. Melatonin, a potent antioxidant, protects against hypoglycemic stress‐induced brain endothelial tight junction injury in the dosage of 400 nmol/L in vitro. FRET (fluorescence resonance energy transfer) imaging data of endothelial cells stressed by low glucose revealed that TIGAR couples with calmodulin to promote TIGAR tyrosine nitration. A tyrosine 92 mutation interferes with the TIGAR‐dependent NADPH generation (55.60% decreased) and abolishes its protective effect on tight junctions in human brain microvascular endothelial cells. We further demonstrate that the low‐glucose‐induced disruption of occludin and Caludin5 as well as activation of autophagy was abrogated by melatonin‐mediated blockade of nitrosative stress in vitro. Collectively, we provide information on the detailed molecular mechanisms for the protective actions of melatonin on brain endothelial tight junctions and suggest that this indole has translational potential for severe hypoglycemia‐induced neurovascular damage.

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“…Cells were grown on glass coverslips in a 24 well plate and fixed in 4% formaldehyde/PBS after indicated treatment for immunofluorescence analysis as previously reported [23]. Cells were fixed in a formaldehyde/ sucrose solution for 10 min and then permeabilized in 0.1% Triton-X solution.…”

Section: Confocal Immunofluorescence Stainingmentioning

confidence: 99%

Elucidation of the FKBP25-60S Ribosomal Protein L7a Stress Response Signaling During Ischemic Injury

Jiang

Yang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Peptidyl-prolyl cis-trans isomerase FKBP25 is a member of the FK506-binding proteins family which has peptidyl-prolyl cis/trans isomerase domain. The biological function and pathophysiologic role of FKBP25 remain elusive. Methods: The spatio-temporal changes in expression of endothelial FKBP25 upon oxygen-glucose deprivation (OGD) treatment were examined by Western blot and immunofluorescence. The immunoprecipitation and fluorescence resonance energy transfer (FRET) were used to address the interacting proteins with FKBP25. Results: In the present study, nuclear translocation of FKBP25 was observed following OGD in cultured endothelial cells. Intriguingly, FKBP25 nuclear translocation was further validated in peroxynitrite (ONOO^-)-treated endothelial cells. Coimmunoprecipitation and FRET data indicated that FKBP25 translocated into the nucleus, in which it interacted with 60S ribosomal protein L7a, while overexpression FKBP25 protect endothelial cells against OGD injury. Conclusion: Our findings reveal that the nuclear import of FKBP25 and binding with 60S ribosomal protein L7a are protective stress responses to ischemia/nitrosaive stress injury.

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Valproic Acid Influences MTNR1A Intracellular Trafficking and Signaling in a β-Arrestin 2-Dependent Manner

Cited by 15 publications

References 51 publications

FXR1P is a GSK3β substrate regulating mood and emotion processing

FXR1P is a GSK3β substrate regulating mood and emotion processing

Melatonin ameliorates hypoglycemic stress‐induced brain endothelial tight junction injury by inhibiting protein nitration of TP53‐induced glycolysis and apoptosis regulator

Elucidation of the FKBP25-60S Ribosomal Protein L7a Stress Response Signaling During Ischemic Injury

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