Fyn arrests swainsonine-induced apoptosis in 293T cells via Akt and its phosphorylation

An, Li; Li, W W; Cheng, Guanchang

doi:10.4238/2015.may.18.23

Cited by 7 publications

(3 citation statements)

References 25 publications

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“…In line with the current bioinformatic findings, previous studies have frequently indicated that FYN is a potential factor that increases Akt activity in mammalian cells, including keratinocytes. FYN has been reported to activate the Akt pathway either through the phosphorylation of tyrosine residues on upstream receptors or by direct phosphorylation of Akt [30][31][32][33]. In this study, we found that the inhibition of FYN negated the effect of DHM on Akt phosphorylation, thus supporting the idea that FYN may play a pivotal role in the Akt regulatory system within keratinocytes.…”

Section: Discussionsupporting

confidence: 83%

Dihydromyrcenol Modulates Involucrin Expression through the Akt Signaling Pathway

Yang,

Kang,

Choi

et al. 2024

IJMS

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The epidermis serves as a protective barrier against external threats and is primarily composed of keratinocytes, which ultimately form corneocytes. Involucrin, a protein integral to the cornified envelope, plays a pivotal role in preserving the functional integrity of the skin barrier. Previous studies have shown that Akt plays an important role in keratinocyte differentiation and skin barrier development. This study investigated whether dihydromyrcenol (DHM), a plant-derived terpene, could increase involucrin production in keratinocytes and sought to elucidate the possible underlying mechanisms. To accomplish this objective, we assessed the alterations in involucrin by DHM through quantitative PCR and Western blot on the HaCaT cell line. The changes in the promoter levels were investigated using luciferase assays. Furthermore, upstream mechanisms were explored through the use of siRNA and inhibitors. To strengthen our findings, the results were subsequently validated in primary cells and 3D skin equivalents. DHM significantly increased involucrin mRNA and protein levels in a concentration-dependent manner. In addition, the Fyn-Akt signaling pathway was found to be required for DHM-induced involucrin expression, as inhibition of Fyn or Akt blocked the increase in involucrin mRNA induced by DHM. The transcription factor Sp1, which is recognized as one of the transcription factors for involucrin, was observed to be activated in response to DHM treatment. Moreover, DHM increased epidermal thickness in a 3D human skin model. These findings suggest that the modulation of involucrin expression with DHM could improve skin barrier function and highlight the importance of manipulating the Akt pathway to achieve this improvement.

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Section: Discussionsupporting

confidence: 83%

Dihydromyrcenol Modulates Involucrin Expression through the Akt Signaling Pathway

Yang,

Kang,

Choi

et al. 2024

IJMS

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“…To determine the signalling transducers between PTPRZ1 and AKT pathway, we examined the previously reported downstream targets of PTPRZ1 in GSCs and matched NSTCs2931. The qRT–PCR results showed that the Src family member Fyn, also an upstream mediator of AKT pathway4748, was preferentially expressed in GSCs relative to NSTCs (Supplementary Fig. 9a).…”

Section: Resultsmentioning

confidence: 99%

Tumour-associated macrophages secrete pleiotrophin to promote PTPRZ1 signalling in glioblastoma stem cells for tumour growth

et al. 2017

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Intense infiltration of tumour-associated macrophages (TAMs) facilitates malignant growth of glioblastoma (GBM), but the underlying mechanisms remain undefined. Herein, we report that TAMs secrete abundant pleiotrophin (PTN) to stimulate glioma stem cells (GSCs) through its receptor PTPRZ1 thus promoting GBM malignant growth through PTN–PTPRZ1 paracrine signalling. PTN expression correlates with infiltration of CD11b+/CD163+ TAMs and poor prognosis of GBM patients. Co-implantation of M2-like macrophages (MLCs) promoted GSC-driven tumour growth, but silencing PTN expression in MLCs mitigated their pro-tumorigenic activity. The PTN receptor PTPRZ1 is preferentially expressed in GSCs and also predicts GBM poor prognosis. Disrupting PTPRZ1 abrogated GSC maintenance and tumorigenic potential. Moreover, blocking the PTN–PTPRZ1 signalling by shRNA or anti-PTPRZ1 antibody potently suppressed GBM tumour growth and prolonged animal survival. Our study uncovered a critical molecular crosstalk between TAMs and GSCs through the PTN–PTPRZ1 paracrine signalling to support GBM malignant growth, indicating that targeting this signalling axis may have therapeutic potential.

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“…Of note, the reduction, inhibition or depletion of Fyn attenuated proinflammatory markers and neuroinflammation [ 42 , 44 , 67 ]. Likewise, activated Fyn is implicated in triggering mitochondrial apoptotic neurodegeneration and cell death [ 38 , 42 , 66 , 68 ]. In our study, we observed less p-Fyn in the PA8-treated 5XFAD mice compared to Trx-treated mice, while there is no change in total Fyn, which indicates that PA8 does not affect basal and total Fyn level, which has a physiological role.…”

Section: Discussionmentioning

confidence: 99%

Peptide aptamer targeting Aβ–PrP–Fyn axis reduces Alzheimer’s disease pathologies in 5XFAD transgenic mouse model

Ali

Arifin

et al. 2023

Cell. Mol. Life Sci.

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Currently, no effective therapeutics exist for the treatment of incurable neurodegenerative diseases such as Alzheimer’s disease (AD). The cellular prion protein (PrPC) acts as a high-affinity receptor for amyloid beta oligomers (AβO), a main neurotoxic species mediating AD pathology. The interaction of AβO with PrPC subsequently activates Fyn tyrosine kinase and neuroinflammation. Herein, we used our previously developed peptide aptamer 8 (PA8) binding to PrPC as a therapeutic to target the AβO–PrP–Fyn axis and prevent its associated pathologies. Our in vitro results indicated that PA8 prevents the binding of AβO with PrPC and reduces AβO-induced neurotoxicity in mouse neuroblastoma N2a cells and primary hippocampal neurons. Next, we performed in vivo experiments using the transgenic 5XFAD mouse model of AD. The 5XFAD mice were treated with PA8 and its scaffold protein thioredoxin A (Trx) at a 14.4 µg/day dosage for 12 weeks by intraventricular infusion through Alzet® osmotic pumps. We observed that treatment with PA8 improves learning and memory functions of 5XFAD mice as compared to Trx-treated 5XFAD mice. We found that PA8 treatment significantly reduces AβO levels and Aβ plaques in the brain tissue of 5XFAD mice. Interestingly, PA8 significantly reduces AβO–PrP interaction and its downstream signaling such as phosphorylation of Fyn kinase, reactive gliosis as well as apoptotic neurodegeneration in the 5XFAD mice compared to Trx-treated 5XFAD mice. Collectively, our results demonstrate that treatment with PA8 targeting the AβO–PrP–Fyn axis is a promising and novel approach to prevent and treat AD.

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Fyn arrests swainsonine-induced apoptosis in 293T cells via Akt and its phosphorylation

Cited by 7 publications

References 25 publications

Dihydromyrcenol Modulates Involucrin Expression through the Akt Signaling Pathway

Dihydromyrcenol Modulates Involucrin Expression through the Akt Signaling Pathway

Tumour-associated macrophages secrete pleiotrophin to promote PTPRZ1 signalling in glioblastoma stem cells for tumour growth

Peptide aptamer targeting Aβ–PrP–Fyn axis reduces Alzheimer’s disease pathologies in 5XFAD transgenic mouse model

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