Differential Regulation of the Renin-Angiotensin System by Nicotine in WKY and SHR Glia

Ferrari, Merari F. R.; Raizada, Mohan K.; Fior-Chadi, Débora Rejane

doi:10.1007/s12031-007-9025-7

Cited by 27 publications

(23 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The expression of iNOS was measured according to an adapted protocol of Ferrari et al [35]. The cells were washed with phosphate saline solution (PBS: NaCl 125 mM, Na 2 HPO 4 2 mM, NaH 2 PO 4 2 mM, KCl 5 mM) and fixed in methanol/acetone (1∶1, 15 min, 20°C).…”

Section: Methodsmentioning

confidence: 99%

The Cellular State Determines the Effect of Melatonin on the Survival of Mixed Cerebellar Cell Culture

Franco

Markus

2014

PLoS ONE

View full text Add to dashboard Cite

The constitutive activation of nuclear factor-κB (NF-κB), a key transcription factor involved in neuroinflammation, is essential for the survival of neurons in situ and of cerebellar granule cells in culture. Melatonin is known to inhibit the activation of NF-κB and has a cytoprotective function. In this study, we evaluated whether the cytoprotective effect of melatonin depends on the state of activation of a mixed cerebellar culture that is composed predominantly of granule cells; we tested the effect of melatonin on cultured rat cerebellar cells stimulated or not with lipopolysaccharide (LPS). The addition of melatonin (0.1 nM–1 µM) reduced the survival of naïve cells while inhibiting LPS-induced cell death. Melatonin (100 nM) transiently (15 min) inhibited the nuclear translocation of both NF-κB dimers (p50/p50, p50/RelA) and, after 60 min, increased the activation of p50/RelA. Melatonin-induced p50/RelA activity in naïve cells resulted in the transcription of inducible nitric oxide synthase (iNOS) and the production of NO. Otherwise, in cultures treated with LPS, melatonin blocked the LPS-induced activation of p50/RelA and the reduction in p50/p50 levels and inhibited iNOS expression and NO synthesis. Therefore, melatonin in vehicle-treated cells induces cell death, while it protects against LPS-induced cytotoxicity. In summary, we confirmed that melatonin is a neuroprotective drug when cerebellar cells are challenged; however, melatonin can also lead to cell death when the normal balance of the NF-κB pathway is disturbed. Our data provide a mechanistic basis for understanding the influence of cell context on the final output response of melatonin.

show abstract

Section: Methodsmentioning

confidence: 99%

The Cellular State Determines the Effect of Melatonin on the Survival of Mixed Cerebellar Cell Culture

Franco

Markus

2014

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…The expression of iNOS protein was determined according to the protocol adapted from Ferrari et al. [18]. Endothelial cells subcultured for up to two passages were seeded onto chamber slide (8 wells) and allowed to grow for 48 hr.…”

Section: Methodsmentioning

confidence: 99%

Melatonin inhibits LPS‐induced NO production in rat endothelial cells

Tamura

Cecon

Monteiro

et al. 2009

Journal of Pineal Research

View full text Add to dashboard Cite

Endothelial cells produce NO by activation of constitutive nitric oxide synthase (NOS) and transcription of inducible NOS (iNOS). We have previously shown that melatonin, in the nanomolar range, inhibits activation of constitutive NOS, and in the present paper, we evaluated whether it could interfere with the expression of iNOS, which is activated by lipopolysaccharide (LPS), a major component of gram-negative bacteria cell walls. Primary cultures of rat endothelial cells were loaded with fluorescent probe for NO detection. Nuclear factor kappa B (NF-kappaB) translocation in endothelial cells elicited by LPS was measured by electromobility shift assay, and the vasodilation of aortic rings was accessed by recording isometric contraction. Melatonin in a micromolar but not in a nanomolar range inhibits the NO production induced by LPS. This effect is not dependent on the activation of G protein-coupled melatonin receptors. The nuclear NF-kappaB translocation is a process necessary for iNOS transcription, and melatonin also inhibits its translocation. LPS induced vasodilation only in endothelium-intact aortic rings, and melatonin (10 mum) inhibits the vasodilation. Here, we show that concentrations compatible with nocturnal melatonin surge (nm) did not interfere with the activity of iNOS. Considering that micromolar melatonin concentrations could be locally achieved through production by activated immune competent cells, extra-pineal melatonin could have a protective effect against tissue injury. We propose that melatonin blocked the LPS-induced vasodilation by inhibiting the NF-kappaB pathway. Finally, we propose that the effect of melatonin on vascular reactivity is one of the mechanisms that underlies the protective effect of this indolamine against LPS.

show abstract

“…The above results indicate that AT 1 R is involved in nicotine-evoked release of both dopamine and norepinephrine, and AT 1 R activation in striatum is counterbalanced by AT 2 R. Furthermore, nicotine exposure alters the expression and activity of the brain RAS. In primary cultures of neurons and glial cells isolated from brainstem and hypothalamus of 1-day-old rats, nicotine treatment resulted in increased expression of AT 1 R but decreased expression of ACE2, and these nicotine effects were greater in cells isolated from spontaneously hypertensive rats compared with Wistar-Kyoto rats (43,44). The above findings provide strong evidence that interaction between nicotine and the brain RAS may contribute to the sympatho-mimetic actions of nicotine as well as AT 1 R-mediated neurogenic hypertension (144).…”

Section: Nicotine and The Ras In The Nervous Systemmentioning

confidence: 96%

Nicotine and the renin-angiotensin system

Oakes

Fuchs

Gardner

et al. 2018

American Journal of Physiology-Regulatory, Integrative and Comp

270

268

View full text Add to dashboard Cite

Cigarette smoking is the single most important risk factor for the development of cardiovascular and pulmonary diseases (CVPD). Although cigarette smoking has been in constant decline since the 1950's, the introduction of e-cigarettes or electronic nicotine delivery systems 10 years ago has attracted former smokers as well as a new generation of consumers. Nicotine is a highly addictive substance, and it is currently unclear whether e-cigarettes are "safer" than regular cigarettes or whether they have the potential to reverse the health benefits, notably on the cardiopulmonary system, acquired with the decline of tobacco smoking. Of great concern, nicotine inhalation devices are becoming popular among young adults and youths, emphasizing the need for awareness and further study of the potential cardiopulmonary risks of nicotine and associated products. This review focuses on the interaction between nicotine and the renin-angiotensin system (RAS), one of the most important regulatory systems on autonomic, cardiovascular and pulmonary functions in both health and disease. The literature presented in this review strongly suggests that nicotine alters the homeostasis of the RAS by up-regulating the detrimental angiotensin converting enzyme (ACE)/Angiotensin (Ang)-II/Ang-II type 1 receptor (ATR) axis and down-regulating the compensatory ACE2/Ang-(1-7)/Mas receptor axis, contributing to the development of CVPD.

show abstract

Differential Regulation of the Renin-Angiotensin System by Nicotine in WKY and SHR Glia

Cited by 27 publications

References 63 publications

The Cellular State Determines the Effect of Melatonin on the Survival of Mixed Cerebellar Cell Culture

The Cellular State Determines the Effect of Melatonin on the Survival of Mixed Cerebellar Cell Culture

Melatonin inhibits LPS‐induced NO production in rat endothelial cells

Nicotine and the renin-angiotensin system

Contact Info

Product

Resources

About