Pituitary Adenylate Cyclase-activating Polypeptide (PACAP) Targets Down Syndrome Candidate Region 1 (DSCR1/RCAN1) to control Neuronal Differentiation

Lee, Eun Hye; Kim, Seon Sook; Lee, Seul; Baek, Kwan-Hyuck; Seo, Su Ryeon

doi:10.1074/jbc.m115.639476

Cited by 5 publications

(5 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, the activity of pituitary adenylate cyclase-activating peptide (PACAP), a neurotrophic peptide involved in nervous system development, learning, and memory, was significantly disturbed by changes in RCAN1 expression [225]. RCAN1 overexpression impaired neurotrophic support of sympathetic neurons by inhibiting TrkA endocytosis, resulting in NGF signaling silencing and associated neurodevelopmental deficits [92].…”

Section: Controversial Roles In Nervous System Diseasesmentioning

confidence: 99%

“…Considering that RCAN1 overexpression is a hallmark of Down syndrome [ 219 , 222 ], it can be hypothesized that this event also contributes to the pathogenesis of AD-like neuropathology typically observed in Down syndrome patients after their middle age [ 223 , 224 ]. In addition, the activity of pituitary adenylate cyclase-activating peptide (PACAP), a neurotrophic peptide involved in nervous system development, learning, and memory, was significantly disturbed by changes in RCAN1 expression [ 225 ]. RCAN1 overexpression impaired neurotrophic support of sympathetic neurons by inhibiting TrkA endocytosis, resulting in NGF signaling silencing and associated neurodevelopmental deficits [ 92 ].…”

Section: Controversial Roles In Nervous System Diseasesmentioning

confidence: 99%

See 1 more Smart Citation

The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and Diseases

Kipanyula

Kimaro

Etet

2016

Journal of Aging Research

View full text Add to dashboard Cite

The ongoing epidemics of metabolic diseases and increase in the older population have increased the incidences of neurodegenerative diseases. Evidence from murine and cell line models has implicated calcineurin-nuclear factor of activated T-lymphocytes (NFAT) signaling pathway, a Ca2+/calmodulin-dependent major proinflammatory pathway, in the pathogenesis of these diseases. Neurotoxins such as amyloid-β, tau protein, and α-synuclein trigger abnormal calcineurin/NFAT signaling activities. Additionally increased activities of endogenous regulators of calcineurin like plasma membrane Ca2+-ATPase (PMCA) and regulator of calcineurin 1 (RCAN1) also cause neuronal and glial loss and related functional alterations, in neurodegenerative diseases, psychotic disorders, epilepsy, and traumatic brain and spinal cord injuries. Treatment with calcineurin/NFAT inhibitors induces some degree of neuroprotection and decreased reactive gliosis in the central and peripheral nervous system. In this paper, we summarize and discuss the current understanding of the roles of calcineurin/NFAT signaling in physiology and pathologies of the adult and developing nervous system, with an emphasis on recent reports and cutting-edge findings. Calcineurin/NFAT signaling is known for its critical roles in the developing and adult nervous system. Its role in physiological and pathological processes is still controversial. However, available data suggest that its beneficial and detrimental effects are context-dependent. In view of recent reports calcineurin/NFAT signaling is likely to serve as a potential therapeutic target for neurodegenerative diseases and conditions. This review further highlights the need to characterize better all factors determining the outcome of calcineurin/NFAT signaling in diseases and the downstream targets mediating the beneficial and detrimental effects.

show abstract

Section: Controversial Roles In Nervous System Diseasesmentioning

confidence: 99%

Section: Controversial Roles In Nervous System Diseasesmentioning

confidence: 99%

The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and Diseases

Kipanyula

Kimaro

Etet

2016

Journal of Aging Research

View full text Add to dashboard Cite

show abstract

“…As shown in Figure 3 A, CA extract (1 and 10 μg/mL) caused an increase in RCAN1 mRNA levels in RAW264.7 cells. To further investigate CA-dependent RCAN1 transcription, we used the RCAN1-reporter construct, which contains a promoter of the RCAN1 gene [ 21 ]. CA induced an increase in RCAN1 promoter activity compared with untreated cells ( Figure 3 B).…”

Section: Resultsmentioning

confidence: 99%

“…The series of RCAN1 shRNA expression vectors was purchased from Origene (Rockville, MD, USA). The reporter gene RCAN1-Luc was previously described [ 21 ].…”

Section: Methodsmentioning

confidence: 99%

Cynanchi atrati and Its Phenolic Constituent Sinapic Acid Target Regulator of Calcineurin 1 (RCAN1) to Control Skin Inflammation

Kim

Kim²,

Seo

2022

Antioxidants

Self Cite

View full text Add to dashboard Cite

Atopic dermatitis (AD) is a common inflammatory skin disorder, and numerous pharmacological approaches are employed to reduce symptoms. Natural products of plant-derived materials have been accepted as complementary therapy for the treatment of a wide range of inflammatory diseases. Cynanchi atrati (CA) is an oriental medicinal herb used in the treatment of acute urinary infection, febrile diseases, and laryngopharyngitis. However, the role of CA root extract in skin inflammation such as AD has not been explored yet. In this study, we examined the possible effect of CA root extract on skin inflammation and evaluated the underlying signaling mechanism using in vitro and in vivo modeling systems. Raw264.7 macrophages were used for in vitro experiments, and an oxazolone-induced AD mouse model was used to evaluate in vivo effects. CA extract significantly inhibited the expression levels of lipopolysaccharide (LPS)-induced pro-inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-1β (IL-1β) in RAW264.7 macrophages. The CA root extract mediated suppression of pro-inflammatory cytokine expression and was associated with the decreased nuclear factor kappa B (NF-κB) gene transcriptional activation. Moreover, CA root extract attenuated the in vivo expression of IL-6 and tumor necrosis factor-α (TNF-α) and ear swelling in the AD mouse models. We also observed that the inhibitory effect of CA root extract on skin inflammation was accompanied by the upregulation of calcineurin 1 (RCAN1) expression, which functions in the inflammatory pathways by suppressing NF-κB signaling. We consistently observed that the immunosuppressive effect of CA root extract in AD was significantly perturbed in the RCAN1 knockout mice. In addition, we isolated a phenolic acid compound, sinapic acid (SA), from the CA root extract and found that SA consistently exerted an immunosuppressive effect in RAW264.7 macrophages by inducing RCAN1 expression. Our results provide the first evidence that CA root extract and its phenolic acid constituent, SA, modulate NF-κB signaling pathways by inducing RCAN1 expression in the skin inflammation process. Thus, we suggest that CA root extract has a therapeutic value for the treatment of AD by targeting endogenous immune regulators.

show abstract

“…Since their establishment, PC12 cells have been widely disseminated and force is to note that, from 1 article to the other, the cells exhibit very variable morphologies [16][17][18][19]. This suggests that through the passages and according to culture conditions, PC12 cells have evolved differently in the numerous laboratories where they are disseminated worldwide.…”

Section: Introductionmentioning

confidence: 99%

The Heterogeneity of Response of PC12 Cells from Different Laboratories to Nerve Growth Factor and Pituitary Adenylate Cyclase-Activating Polypeptide Questions the Reproducibility of Studies Carried Out with Tumor Cell Lines

et al. 2021

View full text Add to dashboard Cite

Background: PC12 pheochromocytoma tumor cell lines are widely used to decipher the intracellular signaling mechanisms mediating the effects of some growth factors. Nevertheless, the disparity in appearance of some PC12 cell lines used in the different publications questions our ability to compare the results obtained by the numerous laboratories which use them. This led us to analyze the phenotypic aspect and transcriptomic expression of 5 PC12 cell lines from different origins under control conditions and after treatment with nerve growth factor (NGF) or pituitary adenylate cyclase-activating polypeptide (PACAP). Methods: Characterization of the 5 PC12 cell lines was conducted using imaging techniques and high-throughput real-time PCR combined with bioinformatics analysis. Results: The results show that the 5 cell lines are very variable in terms of shape, proliferation rate, motility, adhesion to the substrate, and gene expression. This high heterogeneity of the cell lines is also found when looking at their response to NGF or PACAP on gene expression or differentiation, with even in some cases opposite effects, as, for example, on cell proliferation. Actually, only 2 of the cell lines tested exhibited some phenotypic similarities with each other, even though the transcriptomic analyses show that they are far from identical. Discussion/Conclusion: As this issue of cell heterogenicity is not restricted to PC12 cells, the present results highlight the need to facilitate the supply of cell lines at low cost, the necessity to standardize practices regarding the use of cell lines, and the requirement to define precise markers of established cell lines which should be monitored in every publication. Regarding this latter point, the present data show that transcriptomic analysis by real-time PCR using a panel of genes of interest is easy to implement and provides a reliable method to control the possible drift of the cells over time in culture. Transcriptomic phenotyping combined with bioinformatics analysis can also be a useful approach to predict the response of the cells to treatments in terms of cell signaling activation, which can help to choose among several cell lines the most appropriate one for the investigation of a particular mechanism. Taken together, the results from this study highlight the need to use well-characterized cell lines with standardized protocols to generate reproducible results from 1 laboratory to the other.

show abstract

Pituitary Adenylate Cyclase-activating Polypeptide (PACAP) Targets Down Syndrome Candidate Region 1 (DSCR1/RCAN1) to control Neuronal Differentiation

Cited by 5 publications

References 55 publications

The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and Diseases

The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and Diseases

Cynanchi atrati and Its Phenolic Constituent Sinapic Acid Target Regulator of Calcineurin 1 (RCAN1) to Control Skin Inflammation

The Heterogeneity of Response of PC12 Cells from Different Laboratories to Nerve Growth Factor and Pituitary Adenylate Cyclase-Activating Polypeptide Questions the Reproducibility of Studies Carried Out with Tumor Cell Lines

Contact Info

Product

Resources

About