scholarly journals Cross-talk between androgen receptor/filamin A and TrkA regulates neurite outgrowth in PC12 cells

2015 ◽  
Vol 26 (15) ◽  
pp. 2858-2872 ◽  
Author(s):  
Marzia Di Donato ◽  
Antonio Bilancio ◽  
Loredana D'Amato ◽  
Pamela Claudiani ◽  
Maria Antonietta Oliviero ◽  
...  
Keyword(s):  
Growth Factors ◽  
Androgen Receptor ◽  
Pc12 Cells ◽  
Cross Talk ◽  
Reciprocal Cross ◽  
Neuronal Development ◽  
Β1 Integrin ◽  
Filamin A ◽  
Pathological Conditions ◽  
Ngf Signaling

Steroids and growth factors control neuronal development through their receptors under physiological and pathological conditions. We show that PC12 cells harbor endogenous androgen receptor (AR), whose inhibition or silencing strongly interferes with neuritogenesis stimulated by the nonaromatizable synthetic androgen R1881 or NGF. This implies a role for AR not only in androgen signaling, but also in NGF signaling. In turn, a pharmacological TrkA inhibitor interferes with NGF- or androgen-induced neuritogenesis. In addition, androgen or NGF triggers AR association with TrkA, TrkA interaction with PI3-K δ, and downstream activation of PI3-K δ and Rac in PC12 cells. Once associated with AR, filamin A (FlnA) contributes to androgen or NGF neuritogenesis, likely through its interaction with signaling effectors, such as Rac. This study thus identifies a previously unrecognized reciprocal cross-talk between AR and TrkA, which is controlled by β1 integrin. The contribution of FlnA/AR complex and PI3-K δ to neuronal differentiation by androgens and NGF is also novel. This is the first description of AR function in PC12 cells.

Neuroprotective effect of NDEELNK from sea cucumber ovum against scopolamine-induced PC12 cells damage through enhancing energy metabolism and upregulation of PKA/BDNF/NGF signaling pathway

2021 ◽  
Author(s):  
Yue Zhao ◽  
Yifei Dong ◽  
Qi Ge ◽  
Pengbo Cui ◽  
Na Sun ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Signaling Pathway ◽  
Pc12 Cells ◽  
Sea Cucumber ◽  
Molecular Mechanisms ◽  
Neuroprotective Effect ◽  
Ngf Signaling ◽  
Neuroprotective Function

The aim of study was to evaluate the neuroprotective function of sea cucumber ovum peptides-derived NDEELNK and explore underlying molecular mechanisms. NDEELNK exerted neuroprotective effect by improving the acetylcholine (ACh)...

scholarly journals Androgen-Induced Cell Migration: Role of Androgen Receptor/Filamin A Association

PLoS ONE ◽  
2011 ◽  
Vol 6 (2) ◽  
pp. e17218 ◽  
Author(s):  
Gabriella Castoria ◽  
Loredana D'Amato ◽  
Alessandra Ciociola ◽  
Pia Giovannelli ◽  
Tiziana Giraldi ◽  
...  
Keyword(s):  
Cell Migration ◽  
Androgen Receptor ◽  
Filamin A

scholarly journals MiR-21 is an Ngf-Modulated MicroRNA That Supports Ngf Signaling and Regulates Neuronal Degeneration in PC12 Cells

2014 ◽  
Vol 16 (2) ◽  
pp. 415-430 ◽  
Author(s):  
Enrica Montalban ◽  
Nicola Mattugini ◽  
Roberta Ciarapica ◽  
Claudia Provenzano ◽  
Mauro Savino ◽  
...  
Keyword(s):  
Pc12 Cells ◽  
Neuronal Degeneration ◽  
Ngf Signaling

scholarly journals Antiinflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells

2012 ◽  
Vol 214 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Linda Vignozzi ◽  
Ilaria Cellai ◽  
Raffaella Santi ◽  
Letizia Lombardelli ◽  
Annamaria Morelli ◽  
...  
Keyword(s):  
T Cells ◽  
Growth Factors ◽  
Androgen Receptor ◽  
Benign Prostatic Hyperplasia ◽  
Stromal Cells ◽  
Receptor Activation ◽  
Prostatic Hyperplasia ◽  
Serum Testosterone Level ◽  
Antiinflammatory Effect ◽  
Inflammatory Growth

Progression of benign prostatic hyperplasia (BPH) involves chronic inflammation and immune dysregulation. Preclinical studies have demonstrated that prostate inflammation and tissue remodeling are exacerbated by hypogonadism and prevented by testosterone supplementation. We now investigated whether, in humans, hypogonadism was associated with more severe BPH inflammation and the in vitro effect of the selective androgen receptor agonist dihydrotestosterone (DHT) on cultures of stromal cells derived from BPH patients (hBPH). Histological analysis of inflammatory infiltrates in prostatectomy specimens from a cohort of BPH patients and correlation with serum testosterone level was performed. Even after adjusting for confounding factors, hypogonadism was associated with a fivefold increased risk of intraprostatic inflammation, which was also more severe than that observed in eugonadal BPH patients. Triggering hBPH cells by inflammatory stimuli (tumor necrosis factor α, lipopolysaccharide, or CD4+T cells) induced abundant secretion of inflammatory/growth factors (interleukin 6 (IL6), IL8, and basic fibroblast growth factor (bFGF)). Co-culture of CD4+T cells with hBPH cells induced secretion of Th1 inducer (IL12), Th1-recruiting chemokine (interferon γ inducible protein 10, IP10), and Th2 (IL9)- and Th17 (IL17)-specific cytokines. Pretreatment with DHT inhibited NF-κB activation and suppressed secretion of several inflammatory/growth factors, with the most pronounced effects on IL8, IL6, and bFGF. Reduced inflammatory cytokine production by testosterone cells, an increase in IL10, and a significant reduction of testosterone cells proliferation suggested that DHT exerted a broad antiinflammatory effect on testosterone cells. In conclusion, our data demonstrate that DHT exerts an immune regulatory role on human prostatic stromal cells, inhibiting their potential to actively induce and/or sustain autoimmune and inflammatory responses.

scholarly journals Transcription of Nrdp1 by the androgen receptor is regulated by nuclear filamin A in prostate cancer

2015 ◽  
Vol 22 (3) ◽  
pp. 369-386 ◽  
Author(s):  
Rosalinda M Savoy ◽  
Liqun Chen ◽  
Salma Siddiqui ◽  
Frank U Melgoza ◽  
Blythe Durbin-Johnson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Ubiquitin Ligase ◽  
Scaffolding Protein ◽  
Filamin A ◽  
Androgen Response Element ◽  
Castration Resistant ◽  
Suppression Mechanism ◽  
Transcription Expression ◽  
Transcription Program

Prostate cancer (PCa) progression is regulated by the androgen receptor (AR); however, patients undergoing androgen-deprivation therapy (ADT) for disseminated PCa eventually develop castration-resistant PCa (CRPC). Results of previous studies indicated thatAR, a transcription factor, occupies distinct genomic loci in CRPC compared with hormone-naïve PCa; however, the cause of this distinction was unknown. The E3 ubiquitin ligaseNrdp1is a model AR target modulated by androgens in hormone-naïve PCa but not in CRPC. UsingNrdp1, we investigated how AR switches transcription programs during CRPC progression. The proximalNrdp1promoter contains an androgen response element (ARE); we demonstrated AR binding to this ARE in androgen-sensitive PCa. Analysis of hormone-naive human prostatectomy specimens revealed correlation betweenNrdp1and AR expression, supporting AR regulation of NRDP1 levels in androgen-sensitive tissue. However, despite sustained AR levels, AR binding to theNrdp1promoter andNrdp1expression were suppressed in CRPC. Elucidation of the suppression mechanism demonstrated correlation of NRDP1 levels with nuclear localization of the scaffolding protein filamin A (FLNA) which, as we previously showed, is itself repressed following ADT in many CRPC tumors. Restoration of nuclear FLNA in CRPC stimulated AR binding toNrdp1ARE, increased its transcription, and augmented NRDP1 protein expression and responsiveness to ADT, indicating that nuclear FLNA controls AR-mediated androgen-sensitiveNrdp1transcription. Expression of other AR-regulated genes lost in CRPC was also re-established by nuclear FLNA. Thus, our results indicate that nuclear FLNA promotes androgen-dependent AR-regulated transcription in PCa, while loss of nuclear FLNA in CRPC alters the AR-regulated transcription program.

scholarly journals 566 The cross-talk between lipid mediators and growth factors in the control of wound healing

2016 ◽  
Vol 136 (9) ◽  
pp. S257
Author(s):  
G. Cardinali ◽  
D. Kovacs ◽  
V. Maresca ◽  
O. Sasso ◽  
D. Piomelli ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factors ◽  
Cross Talk ◽  
Lipid Mediators ◽  
The Cross
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