Induction of nitric oxide synthase and heme oxygenase activities by endotoxin in the rat adrenal cortex: involvement of both signaling systems in the modulation of ACTH-dependent steroid production

Grion, N; Repetto, Esteban Martín; Pomeraniec, Y; Calejman, Camila Martínez; Astort, Francisco; Sánchez, Rocío; Pignataro, Omar Pedro; Arias, Pablo; Cymeryng, Cora

doi:10.1677/joe-06-0199

Cited by 17 publications

(26 citation statements)

References 42 publications

(48 reference statements)

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“…Besides the different potencies there are other mechanisms that may account for differences between the way of action of these gaseous messengers such as location (377), biological half-life (403). In general, the HO/CO pathway inhibits the NOS/NO pathway (134), whereas NOS/NO stimulates HO activity (183). Furthermore, it has been suggested that the bioavailability of these gases differ in the microenvironment (38).…”

Section: Role Of Co In Thermoregulation and Fevermentioning

confidence: 99%

Gaseous Mediators in Temperature Regulation

Branco

Soriano

Steiner

2014

Comprehensive Physiology

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Deep body temperature (Tb) is kept relatively constant despite a wide range of ambient temperature variation. Nevertheless, in particular situations it is beneficial to decrease or to increase Tb in a regulated manner. Under hypoxia for instance a regulated drop in Tb (anapyrexia) is key to reduce oxygen demand of tissues when oxygen availability is diminished, leading to an increased survival rate in a number of species when experiencing low levels of inspired oxygen. On the other hand, a regulated rise in Tb (fever) assists the healing process. These regulated changes in Tb are mediated by the brain, where afferent signals converge and the most important regions for the control of Tb are found. The brain (particularly some hypothalamic structures located in the preoptic area) modulates efferent activities that cause changes in heat production (modulating brown adipose tissue activity and perfusion, for instance) and heat loss (modulating tail skin vasculature blood flow, for instance). This review highlights key advances about the role of the gaseous neuromodulators nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) in thermoregulation, acting both on the brain and the periphery.

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Section: Role Of Co In Thermoregulation and Fevermentioning

confidence: 99%

Gaseous Mediators in Temperature Regulation

Branco

Soriano

Steiner

2014

Comprehensive Physiology

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“…), thus allowing the cells to avoid an unregulated steroidogenic response. In fact, we have previously demonstrated that inhibition of HO-1 expression or activity results in significantly higher steroid levels in both Y1 cells and rats (Pomeraniec et al 2004, Grion et al 2007.…”

Section: Discussionmentioning

confidence: 94%

“…Heme oxygenase activity has been also involved in the modulation of steroid production. By attenuating the hormone-induced glucocorticoid response, heme oxygenase activity has been recently included among the modulatory systems involved in the fine-tuning regulation of adrenal steroidogenesis (Pomeraniec et al 2004, Grion et al 2007, Astort et al 2009). …”

Section: Introductionmentioning

confidence: 99%

Role of CREB on heme oxygenase-1 induction in adrenal cells: involvement of the PI3K pathway

Astort

Repetto

Rocha-Viegas

et al. 2016

Journal of Molecular Endocrinology

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In addition to the well-known function of ACTH as the main regulator of adrenal steroidogenesis, we have previously demonstrated its effect on the transcriptional stimulation of HO-1 expression, a component of the cellular antioxidant defense system. In agreement, we hereby demonstrate that, in adrenocortical Y1 cells, HO-1 induction correlates with a significant prevention of the generation of reactive oxygen species induced by H 2 O 2 /Fe 2+ . ACTH/cAMP-dependent activation of redox-imbalanced related factors such as NRF2 or NFκB and the participation of MAPKs in this mechanism was, however, discarded based on results with specific inhibitors and reporter plasmids. We suggest the involvement of CREB in HO-1 induction by ACTH/cAMP, as transfection of cells with a dominant-negative isoform of CREB (DN-CREB-M1) decreased, while overexpression of CREB increased HO-1 protein levels. Sequence screening of the murine HO-1 promoter revealed CRE-like sites located at −146 and −37 of the transcription start site and ChIP studies indicated that this region recruits phosphorylated CREB (pCREB) upon cAMP stimulation in Y1 cells. In agreement, H89 (PKA inhibitor) or cotransfection with DN-CREB-M1 prevented the 8Br-cAMP-dependent increase in luciferase activity in cells transfected with pHO-1[−295/+74].LUC. ACTH and cAMP treatment induced the activation of the PI3K/Akt signaling pathway in a PKA-independent mechanism. Inhibition of this pathway prevented the cAMP-dependent increase in HO-1 protein levels and luciferase activity in cells transfected with pHO-1[−295/+74].LUC. Finally, here we show a crosstalk between the cAMP/PKA and PI3K pathways that affects the binding of p-CREB to its cognate element in the murine promoter of the Hmox1 gene. CREB mediates adrenal HO-1 induction by cAMPf astort, e m repetto and others (Gallo-Payet 2016). In turn, stimulation of PKA activity is involved in the phosphorylation and activation of several transcription factors engaged in the transcriptional stimulation of steroidogenic-related genes. Among them, the cAMP response element binding protein (CREB), the GATA-4 binding protein, the steroidogenic factor 1 (SF1) and the CAAT enhancer binding protein (C/EBP) could be included (Manna et al. 2003a,b, Stocco et al. 2005.Glucocorticoid synthesis in the adrenal cortex is a multistep process where mitochondrial and microsomal cytochrome P450 enzymes, mixed function oxidases, catalyze the hydroxylation of steroids and the reduction of O 2 to water. Even under physiological conditions, ACTHstimulated steroidogenesis generates oxidative stress, as incomplete reduction in O 2 leads to the production of reactive oxygen species (ROS), lipoperoxides and other oxygenated species (Hanukoglu 2006, Prasad et al. 2014. To cope with the potentially damaging effects associated with oxidative stress, adrenal cells activate several antioxidant mechanisms (Chinn et al. 2002, Hanukoglu 2006, Battista et al. 2009). Among them, we have previously shown that the ACTH-dependent induction of heme oxygenase...

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“…Moreover, differences in microenvironment (Hartsfield, 2002), localization (Verma et al 1993) and biological half‐lives (Zhuo et al 1993) may also account for the opposite effects observed also in other areas of the brain. In addition, it has been reported that the haem oxygenase–CO system directly and indirectly inhibits NOS/NO (Hartsfield, 2002; Yang & Qin, 2004; Grion et al 2007). The putative cross‐talk between NO and CO in the LC remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Propyretic role of the locus coeruleus nitric oxide pathway

Soriano

Ravanelli

Batalhão

et al. 2010

Experimental Physiology

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Nitric oxide has been reported to modulate fever in the brain. However, the sites where NO exerts this modulation remain somewhat unclear. Locus coeruleus (LC) neurons express not only nitric oxide synthase (NOS) but also soluble guanylyl cyclase (sGC). In the present study, we evaluated in vivo and ex vivo the putative role of the LC NO-cGMP pathway in fever. To this end, deep body temperature was measured before and after pharmacological modulations of the pathway. Moreover, nitrite/nitrate (NOx) and cGMP levels in the LC were assessed. Conscious rats were microinjected within the LC with a non-selective NOS inhibitor (N G -monomethyl-l-arginine acetate), a NO donor (NOC12), a sGC inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) or a cGMP analogue (8-bromo-cGMP) and injected intraperitoneally with endotoxin. Inhibition of NOS or sGC before endotoxin injection significantly increased the latency to the onset of fever. During the course of fever, inhibition of NOS or sGC attenuated the febrile response, whereas microinjection of NOC12 or 8-bromo-cGMP increased the response. These findings indicate that the LC NO-cGMP pathway plays a propyretic role. Furthermore, we observed a significant increase in NOx and cGMP levels, indicating that the febrile response to endotoxin is accompanied by stimulation of the NO-cGMP pathway in the LC.

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Induction of nitric oxide synthase and heme oxygenase activities by endotoxin in the rat adrenal cortex: involvement of both signaling systems in the modulation of ACTH-dependent steroid production

Cited by 17 publications

References 42 publications

Gaseous Mediators in Temperature Regulation

Gaseous Mediators in Temperature Regulation

Role of CREB on heme oxygenase-1 induction in adrenal cells: involvement of the PI3K pathway

Propyretic role of the locus coeruleus nitric oxide pathway

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