Distinct Molecular Effects of Angiotensin II and Angiotensin III in Rat Astrocytes

Clark, Michelle; Nguyen, Chinh Duc; Tran, Hieu

doi:10.1155/2013/782861

Cited by 12 publications

(6 citation statements)

References 30 publications

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“…Our lab has previously reported the presence of functional astroglial AT1Rs in the brainstem and cerebellum of normotensive rats (Clark et al . , ; Kandalam and Clark ). Ang II via the AT1R can activate several signaling pathways that are critical to astrocyte functions such as regulation of inflammation (Kandalam and Clark ) and proliferation (Clark et al .…”

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confidence: 97%

Heterologous regulation of the cannabinoid type 1 receptor by angiotensin II in astrocytes of spontaneously hypertensive rats

Haspula

Clark

2016

Journal of Neurochemistry

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Brainstem and cerebellar astrocytes have critical roles to play in hypertension and attention-deficit hyperactivity disorder, respectively. Angiotensin (Ang) II, via the astroglial Ang type 1 receptor (AT1R), has been demonstrated to elevate pro-inflammatory mediators in the brainstem and the cerebellum. The activation of astroglial cannabinoid type 1 receptor (CB1R), a master regulator of homeostasis, has been shown to neutralize inflammatory states. Factors that drive disease progression are known to alter the expression of CB1Rs. In this study, we investigated the role of Ang II in regulating CB1R protein and mRNA expression in astrocytes isolated from the brainstem and the cerebellum of spontaneously hypertensive rats (SHRs). The results were then compared with their normotensive counterpart, Wistar rats. Not only was the basal expression of CB1R protein and mRNA significantly lower in SHR brainstem astrocytes, but treatment with Ang II resulted in lowering it further in the initial 12 h. In the case of cerebellum, Ang II up-regulated the CB1R protein and mRNA in SHR astrocytes. While the effect of Ang II on CB1R protein was predominantly mediated via the AT1R in SHR brainstem; both AT1R- and AT2R-mediated Ang II's effect in the SHR cerebellum. These data are strongly indicative of a potential new mode of cross-talk between components of the renin angiotensin system and the endocannabinoid system in astrocytes. The consequence of such a cross-talk could be a potential reduced endocannabinoid tone in brainstem in hypertensive states, but not in the cerebellum under the same conditions.

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confidence: 97%

Heterologous regulation of the cannabinoid type 1 receptor by angiotensin II in astrocytes of spontaneously hypertensive rats

Haspula

Clark

2016

Journal of Neurochemistry

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“…In previous studies, we have established the roles of Ang III in cultured astrocytes isolated from neonatal rat pups. We demonstrated that Ang III, similarly to Ang II, stimulated mitogen activated protein kinases (MAPKs) as well as the JAK2/STAT3 signaling pathways, leading to astrocyte proliferation [8,12,20,21,22,23]. Additionally, Ang III increased IL-6 secretion and the expression of IL-6 mRNA through activation of the JAK2/STAT3 cascade, suggesting pro-inflammatory effects of the peptide [8].…”

Section: Discussionmentioning

confidence: 99%

Angiotensin III Induces JAK2/STAT3 Leading to IL-6 Production in Rat Vascular Smooth Muscle Cells

Alanazi

Clark

2019

IJMS

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The Janus kinase-2/ signal transducer and activators of transcription-3 (JAK2/STAT3) pathway and interleukin-6 (IL-6) are pleiotropic signal transduction systems that are responsible for induction of many cytokines and growth factors. It is unknown whether the renin angiotensin aldosterone system (RAAS) peptide, angiotensin (Ang) III induces JAK2/STAT3 and IL-6 in vascular smooth muscle cells (VSMCs). Thus, the purpose of this study was to investigate whether Ang III induces the JAK2/STAT3 pathway leading to IL-6 production in cultured VSMCs isolated from Wistar rats and determine whether differences exist in spontaneously hypertensive rat (SHR) VSMCs. We gauged Ang III’s effects on this pathway by measuring its action on STAT3 as well as IL-6 production. Ang III behaved similarly as Ang II in stimulation of STAT3 phosphorylation in Wistar and SHR VSMCs. Moreover, there were no differences in this Ang III effect in SHR versus Wistar VSMCs. In Wistar VSMCs, Ang II and Ang III significantly induced IL-6 protein secretion and mRNA expression. However, IL-6 protein secretions mediated by these peptides were significantly greater in SHR VSMCs. Ang III induced the JAK2/STAT3 pathway, leading to IL-6 protein secretion and IL-6 mRNA expression via actions on AT1Rs. Moreover, the actions of Ang III to induce IL-6 production was dysregulated in SHR VSMCs. These findings suggest that Ang III acts on AT1Rs to induce JAK2/STAT3, leading to an increase in IL-6 in cultured VSMCs. These findings are important in establishing Ang III as an important physiologically relevant peptide in VSMCs.

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“…Three hundred nano mole per liter insulin was added 5 min prior to assay start. To protect AngII from cleavage, incubations were conducted in the presence of the aminopeptidase A inhibitor, amastatin (Sigma-Aldrich, Poland) at a concentration of 10 μmol/L ( 26 , 27 ). Thirty min before the start of measurement, media was replaced by reaction media (RM) containing RPMI 1640 supplemented with 0.5, 1.0, 5.6, or 30 mmol/L glucose.…”

Section: Methodsmentioning

confidence: 99%

Angiotensin II Modulates Podocyte Glucose Transport

et al. 2018

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Podocytes play a central role in the maintenance of the glomerular filtration barrier and are cellular targets of angiotensin II (AngII). Non-hemodynamic pathways of AngII signaling regulate cellular function and mediate podocyte abnormalities that are associated with various glomerulopathies, including diabetic kidney disease. In this study we investigated the capacity of AngII to modulate glucose uptake in mouse podocytes expressing the human AT1 receptor (AT1R+) after 5 days of exposure to normal (NG, 5.6 mmol/L) or to high (HG, 30 mmol/L) glucose. Short (30 min) as well as long-term (24 h) incubations with AngII markedly enhanced glucose transport in both NG and HG cells. In podocytes cultured under NG conditions, AngII inhibited insulin-stimulated glucose uptake. Regardless of the presence or absence of AngII, no effect of insulin on glucose uptake was observed in HG cells. Stimulation of glucose transport by AngII was mediated by protein kinase C and by phosphoinositide 3-kinase. Glucose dependent surface expression of the glucose transporters GLUT1, GLUT2, and GLUT4 was modulated by AngII in a time and glucose concentration dependent manner. Furthermore, despite its inhibitory effect on insulin's action, AngII elevated the number of podocyte insulin receptors in both NG and HG cultured cells. These findings demonstrate that AngII modulates podocyte basal, as well as insulin-dependent glucose uptake by regulating glucose transporters and insulin signaling.

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Distinct Molecular Effects of Angiotensin II and Angiotensin III in Rat Astrocytes

Cited by 12 publications

References 30 publications

Heterologous regulation of the cannabinoid type 1 receptor by angiotensin II in astrocytes of spontaneously hypertensive rats

Heterologous regulation of the cannabinoid type 1 receptor by angiotensin II in astrocytes of spontaneously hypertensive rats

Angiotensin III Induces JAK2/STAT3 Leading to IL-6 Production in Rat Vascular Smooth Muscle Cells

Angiotensin II Modulates Podocyte Glucose Transport

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