Coupling of angiotensin II AT1 receptors to neuronal NHE activity and carrier-mediated norepinephrine release in myocardial ischemia

2004 ◽  
Vol 286 (4) ◽  
pp. H1448-H1454 ◽  
Author(s):  
Alicia C. Reid ◽  
Christina J. Mackins ◽  
Nahid Seyedi ◽  
Roberto Levi ◽  
Randi B. Silver
Keyword(s):  
Angiotensin Ii ◽  
Myocardial Ischemia ◽  
Neuroblastoma Cells ◽  
Ang Ii ◽  
Cardiac Sympathetic Nerve ◽  
Norepinephrine Release ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
At1 Receptors ◽  
Dependent Pathway

In ischemia, cardiac sympathetic nerve endings (cSNE) release excessive amounts of norepinephrine (NE) via the nonexocytotic Na+-dependent NE transporter (NET). NET, normally responsible for NE reuptake into cSNE, reverses in myocardial ischemia, releasing pathological amounts of NE. This carrier-mediated NE release can be triggered by elevated intracellular Na+ levels in the axoplasm. The fact that ischemia activates the intracellular pH regulatory Na+/H+ exchanger (NHE) in cSNE is pivotal in increasing intraneuronal Na+ and thus activating carrier-mediated NE release. Angiotensin (ANG) II levels are also significantly elevated in the ischemic heart. However, the effects of ANG II on cSNE, which express the ANG II receptor, AT1R, are poorly understood. We hypothesized that ANG II-induced AT1R activation in cSNE may be positively coupled to NHE activity and thereby facilitate the pathological release of NE associated with myocardial ischemia. We tested this hypothesis in a cSNE model, human neuroblastoma cells stably transfected with rat recombinant AT1A receptor (SH-SY5Y-AT1A). SH-SY5Y-AT1A constitutively expresses amiloride-sensitive NHE and the NET. NHE activity was assayed in BCECF-loaded SH-SY5Y-AT1A as the rate of the Na+-dependent alkalinization in response to an acute acidosis. ANG II activation of AT1R markedly increased NHE activity in SH-SY5Y-AT1A via a Ca2+-dependent pathway and promoted carrier-mediated NE release. In addition, in guinea pig cSNE expressing native AT1R, ANG II elicited carrier-mediated NE release. In SH-SY5Y-AT1A and cSNE, amiloride inhibited the ANG II-mediated release of NE. Our results provide a link between AT1R and NHE in cSNE, which can exacerbate carrier-mediated NE release during protracted myocardial ischemia.

scholarly journals Angiotensin II Induces Differentiation of Human Neuroblastoma Cells by Increasing MAP2 and ROS Levels

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Bryan Jael Collazo ◽  
Dariana Morales-Vázquez ◽  
Jaylene Álvarez-Del Valle ◽  
Javier E. Sierra ◽  
Juan Carlos Medina ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Nadph Oxidase ◽  
Cell Size ◽  
Neuroblastoma Cells ◽  
Ang Ii ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Simultaneous Activation ◽  
Atr Activation ◽  
In Cells

Introduction. The roles of angiotensin II (Ang II) in the brain are still under investigation. In this study, we investigated if Ang II influences differentiation of human neuroblastoma cells with simultaneous activation of NADPH oxidase and reactive oxygen species (ROS). Moreover, we investigated the Ang II receptor type involved during differentiation. Methods. Human neuroblastoma cells (SH-SY5Y; 5 × 10 5 cells) were exposed to Ang II (600 nM) for 24 h. Differentiation was monitored by measuring MAP2 and NF-H levels. Cell size and ROS were analyzed by flow cytometry, and NADPH oxidase activation was assayed using apocynin (500 μM). Ang II receptors (ATR) activation was assayed using ATR blockers or Ang II metabolism inhibitors (10-7 M). Results. (1) Cell size decreased significantly in Ang II-treated cells; (2) MAP2 and ROS increased significantly in Ang II-treated cells with no changes in viability; (3) MAP2 and ROS decreased significantly in cells incubated with Ang II plus apocynin. (4) A significant decrease in MAP2 was observed in cells exposed to Ang II plus PD123.319 (AT2R blocker). Conclusion. Our findings suggest that Ang II influences differentiation of SH-SY5Y by increasing MAP2 through the AT2R. The increase in MAP2 and ROS were also mediated through NADPH oxidase with no cell death.

Identification and characterization of functional angiotensin II receptors in human neuroblastoma cells

1995 ◽  
Vol 56 (2-3) ◽  
pp. 175-184 ◽  
Author(s):  
Mario Maggi ◽  
Giovanna Finetti ◽  
Anna Cioni ◽  
Rosa Mancina ◽  
Elisabetta Baldi ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Neuroblastoma Cells ◽  
Angiotensin Ii Receptors ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Identification And Characterization

Oleacein inhibits STAT3, activates the apoptotic machinery, and exerts anti-metastatic effects in the SH-SY5Y human neuroblastoma cells

2020 ◽  
Vol 11 (4) ◽  
pp. 3271-3279 ◽  
Author(s):  
Santa Cirmi ◽  
Marilena Celano ◽  
Giovanni Enrico Lombardo ◽  
Valentina Maggisano ◽  
Antonio Procopio ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Olive Oil ◽  
Neuroblastoma Cells ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Apoptotic Death ◽  
Cell Adhesion And Migration ◽  
And Migration ◽  
Dependent Pathway

The present findings demonstrate that oleacein, the main secoiridoid of extravirgin olive oil, acts against neuroblastoma cells, by reducing cell adhesion and migration, inducing apoptotic death and modulating STAT3-dependent pathway.

scholarly journals 4-Hydroxychalcone Induces Cell Death via Oxidative Stress in MYCN-Amplified Human Neuroblastoma Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Amnah M. Alshangiti ◽  
Eszter Tuboly ◽  
Shane V. Hegarty ◽  
Cathal M. McCarthy ◽  
Aideen M. Sullivan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Cytotoxic Effect ◽  
Neuroblastoma Cells ◽  
Reactive Oxygen ◽  
Prognostic Indicator ◽  
Oxygen Species ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma

Neuroblastoma is an embryonal malignancy that arises from cells of sympathoadrenal lineage during the development of the nervous system. It is the most common pediatric extracranial solid tumor and is responsible for 15% of childhood deaths from cancer. Fifty percent of cases are diagnosed as high-risk metastatic disease with a low overall 5-year survival rate. More than half of patients experience disease recurrence that can be refractory to treatment. Amplification of the MYCN gene is an important prognostic indicator that is associated with rapid disease progression and a poor prognosis, highlighting the need for new therapeutic approaches. In recent years, there has been an increasing focus on identifying anticancer properties of naturally occurring chalcones, which are secondary metabolites with variable phenolic structures. Here, we report that 4-hydroxychalcone is a potent cytotoxin for MYCN-amplified IMR-32 and SK-N-BE (2) neuroblastoma cells, when compared to non-MYCN-amplified SH-SY5Y neuroblastoma cells and to the non-neuroblastoma human embryonic kidney cell line, HEK293t. Moreover, 4-hydroxychalcone treatment significantly decreased cellular levels of the antioxidant glutathione and increased cellular reactive oxygen species. In addition, 4-hydroxychalcone treatment led to impairments in mitochondrial respiratory function, compared to controls. In support of this, the cytotoxic effect of 4-hydroxychalcone was prevented by co-treatment with either the antioxidant N-acetyl-L-cysteine, a pharmacological inhibitor of oxidative stress-induced cell death (IM-54) or the mitochondrial reactive oxygen species scavenger, Mito-TEMPO. When combined with the anticancer drugs cisplatin or doxorubicin, 4-hydroxychalcone led to greater reductions in cell viability than was induced by either anti-cancer agent alone. In summary, this study identifies a cytotoxic effect of 4-hydroxychalcone in MYCN-amplified human neuroblastoma cells, which rationalizes its further study in the development of new therapies for pediatric neuroblastoma.

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