scholarly journals Contributions of Nitric Oxide to AHR-Ligand-Mediated Keratinocyte Differentiation

2020 ◽  
Vol 21 (16) ◽  
pp. 5680
Author(s):  
Carrie Hayes Sutter ◽  
Haley M. Rainwater ◽  
Thomas R. Sutter
Keyword(s):  
Nitric Oxide ◽  
Epithelial Cell ◽  
Cell Fate ◽  
Terminal Differentiation ◽  
Metabolic Reprogramming ◽  
Keratinocyte Differentiation ◽  
Epidermal Keratinocytes ◽  
Nitric Oxide Signaling ◽  
Selective Ligand

Activation of the aryl hydrocarbon receptor (AHR) in normal human epidermal keratinocytes (NHEKs) accelerates keratinocyte terminal differentiation through metabolic reprogramming and reactive oxygen species (ROS) production. Of the three NOS isoforms, NOS3 is significantly increased at both the RNA and protein levels by exposure to the very potent and selective ligand of the AHR, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Inhibition of NOS with the chemical N-nitro-l-arginine methyl ester (l-NAME) reversed TCDD-induced cornified envelope formation, an endpoint of terminal differentiation, as well as the expression of filaggrin (FLG), a marker of differentiation. Conversely, exposure to the NO-donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP), increased the number of cornified envelopes above control levels and augmented the levels of cornified envelopes formed in response to TCDD treatment and increased the expression of FLG. This indicates that nitric oxide signaling can increase keratinocyte differentiation and that it is involved in the AHR-mediated acceleration of differentiation. As the nitrosylation of cysteines is a mechanism by which NO affects the structure and functions of proteins, the S-nitrosylation biotin switch technique was used to measure protein S-nitrosylation. Activation of the AHR increased the S-nitrosylation of two detected proteins of about 72 and 20 kD in size. These results provide new insights into the role of NO and protein nitrosylation in the process of epithelial cell differentiation, suggesting a role of NOS in metabolic reprogramming and the regulation of epithelial cell fate.

scholarly journals The role of cathepsin E in terminal differentiation of keratinocytes

2011 ◽  
Vol 392 (6) ◽  
Author(s):  
Tomoyo Kawakubo ◽  
Atsushi Yasukochi ◽  
Kuniaki Okamoto ◽  
Yoshiko Okamoto ◽  
Seiji Nakamura ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Primary Cultures ◽  
Terminal Differentiation ◽  
Epidermal Differentiation ◽  
Keratinocyte Differentiation ◽  
Epidermal Keratinocytes ◽  
Marker Genes ◽  
Differentiation Markers ◽  
Cathepsin E

Abstract Cathepsin E (CatE) is predominantly expressed in the rapidly regenerating gastric mucosal cells and epidermal keratinocytes, in addition to the immune system cells. However, the role of CatE in these cells remains unclear. Here we report a crucial role of CatE in keratinocyte terminal differentiation. CatE deficiency in mice induces abnormal keratinocyte differentiation in the epidermis and hair follicle, characterized by the significant expansion of corium and the reduction of subcutaneous tissue and hair follicle. In a model of skin papillomas formed in three different genotypes of syngeneic mice, CatE deficiency results in significantly reduced expression and altered localization of the keratinocyte differentiation induced proteins, keratin 1 and loricrin. Involvement of CatE in the regulation of the expression of epidermal differentiation specific proteins was corroborated by in vitro studies with primary cultures of keratinocytes from the three different genotypes of mice. In wild-type keratinocytes after differentiation inducing stimuli, the CatE expression profile was compatible to those of the terminal differentiation marker genes tested. Overexpression of CatE in mice enhances the keratinocyte terminal differentiation process, whereas CatE deficiency results in delayed differentiation accompanying the reduced expression or the ectopic localization of the differentiation markers. Our findings suggest that in keratinocytes CatE is functionally linked to the expression of terminal differentiation markers, thereby regulating epidermis formation and homeostasis.

scholarly journals Role of β-Adrenergic Receptors and Nitric Oxide Signaling in Exercise-Mediated Cardioprotection

Physiology ◽  
2013 ◽  
Vol 28 (4) ◽  
pp. 216-224 ◽  
Author(s):  
John W. Calvert ◽  
David J. Lefer
Keyword(s):  
Nitric Oxide ◽  
Risk Factors ◽  
Adrenergic Receptors ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Nitric Oxide Signaling ◽  
Factors Associated ◽  
Cardioprotective Effects ◽  
Β Adrenergic Receptors

Exercise promotes cardioprotection in both humans and animals not only by reducing risk factors associated with cardiovascular disease but by reducing myocardial infarction and improving survival following ischemia. This article will define the role that nitric oxide and β-adrenergic receptors play in mediating the cardioprotective effects of exercise in the setting of ischemia-reperfusion injury.

scholarly journals The Critical Role of 15-Lipoxygenase-1 in Colorectal Epithelial Cell Terminal Differentiation and Tumorigenesis

2005 ◽  
Vol 65 (24) ◽  
pp. 11486-11492 ◽  
Author(s):  
Imad Shureiqi ◽  
Yuanqing Wu ◽  
Dongning Chen ◽  
Xiu L. Yang ◽  
Baoxiang Guan ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Critical Role ◽  
Terminal Differentiation

The role of nitric oxide signaling in renoprotective effects of hydrogen sulfide against chronic kidney disease in rats: Involvement of oxidative stress, autophagy and apoptosis

2018 ◽  
Vol 234 (7) ◽  
pp. 11411-11423 ◽  
Author(s):  
Mohammad Khabbaz Shirazi ◽  
Asaad Azarnezhad ◽  
Mohammad Foad Abazari ◽  
Mansour Poorebrahim ◽  
Pegah Ghoraeian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Chronic Kidney Disease ◽  
Hydrogen Sulfide ◽  
Kidney Disease ◽  
Nitric Oxide Signaling

Endothelial dysfunction induced by cadmium and mercury and its relationship to hypertension

2021 ◽  
Vol 17 ◽  
Author(s):  
Airton Cunha Martins ◽  
Alessanda Antunes Dos Santos ◽  
Ana Carolina B. Almeida Lopes ◽  
Anatoly V. Skalny ◽  
Michael Aschner ◽  
...  
Keyword(s):  
Public Health ◽  
Nitric Oxide ◽  
Heavy Metals ◽  
Endothelial Dysfunction ◽  
Toxic Elements ◽  
Health Concern ◽  
Public Health Concern ◽  
Important Public Health ◽  
Nitric Oxide Signaling

: Hypertension is an important public health concern that affects millions globally, leading to a large number of morbidities and fatalities. The etiology of hypertension is complex and multifactorial, and it involves environmental factors including heavy metals. Indeed, cadmium and mercury are toxic elements commonly distributed in the environment which contribute to hypertension. We aimed to assess the role of cadmium and mercury-induced endothelial dysfunction in the development of hypertension. A narrative review was carried out through database searches. In this review, we discussed the critical roles of cadmium and mercury in the etiology of hypertension and provide new insights into potential mechanisms of their effect, focusing primarily on endothelial dysfunction. Although, the mechanisms by which cadmium and mercury induce hypertension have yet to be completely elucidated, evidence for both implicates impaired nitric oxide signaling in their hypertensive etiology.

Terminal differentiation in keratinocytes involves positive as well as negative regulation by retinoic acid receptors and retinoid X receptors at retinoid response elements

1992 ◽  
Vol 12 (11) ◽  
pp. 4862-4871
Author(s):  
B J Aneskievich ◽  
E Fuchs
Keyword(s):  
Retinoic Acid ◽  
Terminal Differentiation ◽  
Cell Types ◽  
Epidermal Differentiation ◽  
Retinoic Acid Receptors ◽  
Keratinocyte Differentiation ◽  
Epidermal Keratinocytes ◽  
Retinoid X Receptors ◽  
Response Elements ◽  
X Receptors

Terminal differentiation of epidermal keratinocytes is inhibited by 1 microM retinoic acid, a concentration which induces differentiation in a number of cell types, including F9 teratocarcinoma cells. The molecular basis for these opposing retinoid responses is unknown, although retinoic acid receptors (RARs) and retinoid X receptors (RXRs) have been detected in both cell types. When F9 cells are stably transfected with a truncated RAR alpha lacking the E/F domain necessary for ligand binding and RAR/RXR dimerization, action at retinoid response elements is suppressed and cells produce a retinoic acid-resistant phenotype; i.e., they are blocked in differentiation (A. S. Espeseth, S. P. Murphy, and E. Linney, Genes Dev. 3:1647-1656, 1989). If retinoid receptors influence epidermal differentiation only in a negative fashion, then suppression of transactivation at retinoid response elements would be expected to enhance, rather than block, keratinocyte differentiation. In this study, we show that surprisingly, even though constitutive expression of an analogous truncated RAR gamma in keratinocytes specifically suppressed transactivation at retinoid response elements, keratinocytes were blocked, rather than enhanced, in their ability to undergo morphological and biochemical features of differentiation. These findings demonstrate a direct and hitherto unrecognized role for RARs and RXRs in positively as well as negatively regulating epidermal differentiation. Additionally, our studies extend those of Espeseth et al. (Genes Dev. 3:1647-1656, 1989), indicating a novel RAR function independent of the E/F domain.

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