Apelin Receptor Signaling Protects GT1-7 GnRH Neurons Against Oxidative Stress In Vitro

Şişli, Hatice Burcu; Hayal, Taha Bartu; Şenkal, Selinay; Kıratlı, Binnur; Sağraç, Derya; Seçkin, Selin; Özpolat, Murat; Şahi̇n, Fikrettin; Yılmaz, Bayram; Doğan, Ayşegül

doi:10.1007/s10571-020-00968-2

Cited by 10 publications

(6 citation statements)

References 69 publications

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“…Therefore, the expression and activation of the apelin/APJ system in GnRH neurons might support a protective mechanism against oxidative stress-induced cell death. Furthermore, the observation of a promoting effect of the apelinergic system on GnRH release in embryonic stem cell-derived GnRH neurons supports the hypothesis of its pro-differentiating role during developmental stages [159].…”

Section: Oxidative Stress In the Central Nervous Systemsupporting

confidence: 72%

“…Recent evidence suggests that GnRH neurons are targets of apelin-associated neuroprotection. APJ signaling pathway activation via either apelin-13 or transient overexpression is able to increase GnRH neurons proliferation after H 2 O 2 exposure and hypoxia, and to stimulate the conversion of G0/G1 to S phase through AKT and ERK-1/2 kinase pathways activation [159]. Therefore, the expression and activation of the apelin/APJ system in GnRH neurons might support a protective mechanism against oxidative stress-induced cell death.…”

Section: Oxidative Stress In the Central Nervous Systemmentioning

confidence: 99%

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The Yin and Yang Effect of the Apelinergic System in Oxidative Stress

Fibbi

Marroncini

Naldi

et al. 2023

IJMS

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Apelin is an endogenous ligand for the G protein-coupled receptor APJ and has multiple biological activities in human tissues and organs, including the heart, blood vessels, adipose tissue, central nervous system, lungs, kidneys, and liver. This article reviews the crucial role of apelin in regulating oxidative stress-related processes by promoting prooxidant or antioxidant mechanisms. Following the binding of APJ to different active apelin isoforms and the interaction with several G proteins according to cell types, the apelin/APJ system is able to modulate different intracellular signaling pathways and biological functions, such as vascular tone, platelet aggregation and leukocytes adhesion, myocardial activity, ischemia/reperfusion injury, insulin resistance, inflammation, and cell proliferation and invasion. As a consequence of these multifaceted properties, the role of the apelinergic axis in the pathogenesis of degenerative and proliferative conditions (e.g., Alzheimer’s and Parkinson’s diseases, osteoporosis, and cancer) is currently investigated. In this view, the dual effect of the apelin/APJ system in the regulation of oxidative stress needs to be more extensively clarified, in order to identify new potential strategies and tools able to selectively modulate this axis according to the tissue-specific profile.

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Section: Oxidative Stress In the Central Nervous Systemsupporting

confidence: 72%

Section: Oxidative Stress In the Central Nervous Systemmentioning

confidence: 99%

The Yin and Yang Effect of the Apelinergic System in Oxidative Stress

Fibbi

Marroncini

Naldi

et al. 2023

IJMS

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“… 55 Further, studies demonstrated that impaired GnRH production is directly linked to oxidative stress and mitochondrial dysfunction in neurons. 56 , 57 Another significantly enriched pathway is the gap junction that is involved in the pathogenesis of AD and PD. 58 , 59 For instance, Angeli et al, 2020, demonstrated the altered expression of glial gap junction proteins, namely, Cx43, Cx30, and Cx47, in the 5XFAD model of AD, 60 whereas Maulik et al, 2020, concluded that Aβ regulates the gap junction protein connexin 43 in cultured primary astrocytes.…”

Section: Results and Discussionmentioning

confidence: 99%

CREB1^K292 and HINFP^K330 as Putative Common Therapeutic Targets in Alzheimer’s and Parkinson’s Disease

Gupta

Kumar

2021

ACS Omega

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Integration of omics data and deciphering the mechanism of a biological regulatory network could be a promising approach to reveal the molecular mechanism involved in the progression of complex diseases, including Alzheimer’s and Parkinson’s. Despite having an overlapping mechanism in the etiology of Alzheimer’s disease (AD) and Parkinson’s disease (PD), the exact mechanism and signaling molecules behind them are still unknown. Further, the acetylation mechanism and histone deacetylase (HDAC) enzymes provide a positive direction toward studying the shared phenomenon between AD and PD pathogenesis. For instance, increased expression of HDACs causes a decrease in protein acetylation status, resulting in decreased cognitive and memory function. Herein, we employed an integrative approach to analyze the transcriptomics data that established a potential relationship between AD and PD. Data preprocessing and analysis of four publicly available microarray datasets revealed 10 HUB proteins, namely, CDC42, CD44, FGFR1, MYO5A, NUMA1, TUBB4B, ARHGEF9, USP5, INPP5D, and NUP93, that may be involved in the shared mechanism of AD and PD pathogenesis. Further, we identified the relationship between the HUB proteins and transcription factors that could be involved in the overlapping mechanism of AD and PD. CREB1 and HINFP were the crucial regulatory transcription factors that were involved in the AD and PD crosstalk. Further, lysine acetylation sites and HDAC enzyme prediction revealed the involvement of 15 and 27 potential lysine residues of CREB1 and HINFP, respectively. Our results highlighted the importance of HDAC1(K292) and HDAC6(K330) association with CREB1 and HINFP, respectively, in the AD and PD crosstalk. However, different datasets with a large number of samples and wet lab experimentation are required to validate and pinpoint the exact role of CREB1 and HINFP in the AD and PD crosstalk. It is also possible that the different datasets may or may not affect the results due to analysis parameters. In conclusion, our study potentially highlighted the crucial proteins, transcription factors, biological pathways, lysine residues, and HDAC enzymes shared between AD and PD at the molecular level. The findings can be used to study molecular studies to identify the possible relationship in the AD–PD crosstalk.

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“…Cell viability analysis was performed by the 3‐(4,5‐di‐methyl‐thiazol‐2‐yl)−5‐(3‐carboxy‐ methoxy‐phenyl)−2‐(4‐sulfo‐phenyl)−2H tetrazolium (MTS) assay (CellTiter96 AqueousOne Solution; Promega, Southampton, UK) as previously described according to the manufacturer's instructions. [ 24 ] Briefly, MSCs were seeded at a density of 5 × 10 3 cells per well in a 96‐well plate. The next day, media of positive control was replenished with 20% DMSO in culture media.…”

Section: Methodsmentioning

confidence: 99%

The Role of Aplnr Signaling in the Developmental Regulation of Mesenchymal Stem Cell Differentiation from Human Pluripotent Stem Cells

Şişli,

Şenkal Turhan,

Bulut

et al. 2023

Advanced Biology

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Stem cells are invaluable resources for personalized medicine. Mesenchymal stem cells (MSCs) have received great attention as therapeutic tools due to being a safe, ethical, and accessible option with immunomodulatory and controlled differentiation properties. Apelin receptor (Aplnr) signaling is reported to be involved in biological events, including gastrulation, mesoderm migration, proliferation of MSCs. However, the knowledge about the exact role and mechanism of Aplnr signaling during mesoderm and MSCs differentiation is still primitive. The current study aims to unveil the role of Aplnr signaling during mesoderm and MSC differentiation from pluripotent stem cells (PSCs) through peptide/small molecule activation, overexpression, knock down or CRISPR/Cas9 mediated knock out of the pathway components. Morphological changes, gene and protein expression analysis, including antibody array, LC/MS, mRNA/miRNA sequencing, reveal that Aplnr signaling promotes mesoderm commitment possibly via EGFR and TGF‐beta signaling pathways and enhances migration of cells during mesoderm differentiation. Moreover, Aplnr signaling positively regulates MSCs differentiation from hPSCs and increases MSC characteristics and differentiation capacity by regulating pathways, such as EGFR, TGFβ, Wnt, PDGF, and FGF. Osteogenic, chondrogenic, adipogenic, and myogenic differentiations are significantly enhanced with Aplnr signaling activity. This study generates an important foundation to generate high potential MSCs from PSCs to be used in personalized cell therapy.

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Apelin Receptor Signaling Protects GT1-7 GnRH Neurons Against Oxidative Stress In Vitro

Cited by 10 publications

References 69 publications

The Yin and Yang Effect of the Apelinergic System in Oxidative Stress

The Yin and Yang Effect of the Apelinergic System in Oxidative Stress

CREB1^K292 and HINFP^K330 as Putative Common Therapeutic Targets in Alzheimer’s and Parkinson’s Disease

The Role of Aplnr Signaling in the Developmental Regulation of Mesenchymal Stem Cell Differentiation from Human Pluripotent Stem Cells

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Apelin Receptor Signaling Protects GT1-7 GnRH Neurons Against Oxidative Stress In Vitro

Cited by 10 publications

References 69 publications

The Yin and Yang Effect of the Apelinergic System in Oxidative Stress

The Yin and Yang Effect of the Apelinergic System in Oxidative Stress

CREB1K292 and HINFPK330 as Putative Common Therapeutic Targets in Alzheimer’s and Parkinson’s Disease

The Role of Aplnr Signaling in the Developmental Regulation of Mesenchymal Stem Cell Differentiation from Human Pluripotent Stem Cells

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Product

Resources

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CREB1^K292 and HINFP^K330 as Putative Common Therapeutic Targets in Alzheimer’s and Parkinson’s Disease