<i>N</i>‐methyl‐<i>D</i>‐aspartate receptors influence the intracellular calcium concentration of keratinocytes

Fischer, Matthias; Glanz, Dagobert; William, Thomas; Klapperstück, Thomas; Wohlrab, Johannes; Marsch, Wolfgang Ch.

doi:10.1111/j.0906-6705.2004.00200.x

Cited by 31 publications

(33 citation statements)

References 35 publications

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“…Of particular interest, the expression of NMDAR-1 in cutaneous SCC was well correlated with the degree of differentiation of the tumor cells. Selective blockade of NMDAR-1 with MK-801 suppresses the expression of filaggrin and CK10 as differentiation markers in HaCaT cells, but this had no influence on the proliferation of HaCaT cells 7 . This suggests that NMDAR-1 in normal skin plays a role in the differentiation of the epidermis, rather than the proliferation.…”

Section: Discussionmentioning

confidence: 95%

“…Broders' system was used to histologically classify conventional cutaneous SCC by grades 1 to 4 on the basis of the degree of nuclear polymorphism and the cytoplasmic maturation to keratinization 12 . Because many dermatopathologists generally use a variation of this system for investigating the prognostic factors of SCC 5,7 , the presented cases were divided into two subtypes as follows: differentiated SCC with differentiated lesions in about three-fourths or one half of its structure (Broders' grades 1 and 2), and undifferentiated SCC with undifferentiated lesions in about three-fourths of its structure and with no tendency for differentiation (Broders' grades 3 and 4).…”

Section: Subjects and Tissue Specimensmentioning

confidence: 99%

“…Moreover, NMDAR-1 is expressed on keratinocytes 6 . NMDAR-1 expression increased with keratinocytic differentiation in the epidermis of normal human skin and was most intense in the granular cell layers 7 . This receptor distribution correlates well with the intraepidermal calcium gradient in the normal epidermis 8 .…”

Section: Introductionmentioning

confidence: 97%

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The Expression of NMDA Receptor 1 Correlates with Clinicopathological Parameters in Cutaneous Squamous Cell Carcinoma

et al. 2009

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Background: Ionotropic glutamate receptors of the N-methyl-D-aspartate receptor (NMDAR) type are expressed on keratinocytes and play a role in the proliferation, differentiation, and cornification of keratinocytes. However, the expression profile of NMDAR and its role in cutaneous malignancy is unclear. Objective: We analyzed the expression of NMDAR-1 in cutaneous squamous cell carcinoma (SCC) and investigated the relationship between NMDAR-1 expression and clinicopathological parameters. Methods: Thirty-two patients with biopsy-proven cutaneous SCC were enrolled in this study. Each patient was analyzed for tumor diameter, location, local recurrence, and metastasis by conducting a chart review. The SCC specimens were histologically divided into differentiated and undifferentiated groups based on Broders' system. NMDAR-1 expression was examined by performing immunohistochemistry, and the relative staining intensity in the SCCs was graded into 5 levels. According to the staining intensity of NMDAR-1, the specimens were categorized into two groups: the higher group and the lower group. Results: Fifteen (88%) of 17 tumors in the higher group were differentiated SCC, whereas 14 (93%) of 15 tumors in the lower group were undifferentiated SCC. In addition, NMDAR-1 expression was inversely correlated with metastasis (p=0.049). Local recurrence was associated with a lower staining intensity, but the results were not statistically significant. Conclusion: Our results demonstrate that NMDAR-1 expression in cutaneous SCC is significantly correlated with its differentiation and metastasis. Therefore, it may be a prognostic indicator for cutaneous SCC. INTRODUCTIONGlutamate is an essential amino acid and neurotransmitter in the central nervous system (CNS). It plays a major role in excitotoxicity as well as in learning and memory. In addition, it functions as a trophic factor for cancer cells in vitro 1 , suggesting an involvement of glutamate and its receptors in tumor cell proliferation and migration. Glutamate activates various glutamate receptors, including N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, kainite, and metabotropic receptors 2,3 . NMDAR has two distinct subunits: the main subunit, NMDAR-1, and the modulatory subunit, NMDAR 2A-2D. NMDAR-1 is essential and sufficient to form an active NMDA receptor channel, in contrast to the NMDAR-2 subunits 4 . The NMDAR is a ligand-gated ion-channel that is permeable to the cations Na ＋ , K ＋ , and most importantly, Ca 2＋ .Although the expression of the glutamate receptor was initially restricted to the CNS, glutamate signaling occurs in non-neuronal tissues such as bone, pancreas, and skin, raising the possibility of a more widespread glutamate receptor activity 5 . Moreover, NMDAR-1 is expressed on keratinocytes 6 . NMDAR-1 expression increased with keratinocytic differentiation in the epidermis of normal human These results suggest that NMDAR could play a role in the proliferation and differentiation of normal keratinocytes. In ad...

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Section: Discussionmentioning

confidence: 95%

Section: Subjects and Tissue Specimensmentioning

confidence: 99%

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The Expression of NMDA Receptor 1 Correlates with Clinicopathological Parameters in Cutaneous Squamous Cell Carcinoma

et al. 2009

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“…Data suggest that blockade of NMDA receptors in the nervous system by xenon plays a key role in neuroprotective effects of this agent [5,[8][9][10]. Recently, NMDA receptors have been found in the axons of human skin [15] and in the keratinocytes of the epidermis [16,17]. These receptors are involved in skin barrier function [18], calcium regulation [19], and dermatitis development [20].…”

Section: Introductionmentioning

confidence: 99%

Transdermal delivery of xenon from lipophilic solution and water

Verkhovskiy¹,

Atochin²,

Udintsev³

et al. 2015

Dermatol Aspects

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Aim: The purpose of the study was to characterize transdermal delivery of xenon through rat skin from a lipophilic solution and from water. Methods: Sections of skin were obtained from adult rats (n=12) and were placed into static Franz diffusion cells for 24 h. Xenon diffusion coefficients were determined for diffusion from a lipophilic solution (n=6) and from water (n=6) to phosphate buffered saline (PBS) through skin and for diffusion from a lipophilic solution to PBS through a phase boundary in the absence of skin (n=6). Results: Xenon flux (J Xe ) through skin from the lipophilic solution was 0.036 mg/hour×cm 2 and permeability coefficient (K p ) was 0.003 cm/h; J Xe through skin from water was 0.029 mg/h×cm 2 and the K p was 0.002 cm/h. Total time for xenon diffusion through skin from lipophilic solution and from water was ~2 h. Conclusion: The study presents the first characterization of xenon diffusion through rat skin from multiphase solutions to PBS. These data may be useful for the development of xenon-rich pharmaceutical products for external use.

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“…The NMDA-R has been well characterized in the nervous system, as one of the main mediators of excitation (5), but has only recently been found and partially characterized in the skin (6)(7)(8). In normal keratinocytes, the NMDA-R can modulate voltage dependent Ca ++ activity (6) and therefore growth and differentiation of keratinocytes (7,9). Moreover, the expression of the NMDA-R2C subtype is significantly reduced in the basal cell layer of psoriatic skin (2).…”

Section: Introductionmentioning

confidence: 99%

Psoriatic keratinocytes are resistant to tumor necrosis factor alpha's induction of mRNA for the NMDA‐R2C subunit

Morhenn

Nahm

Mansbridge

2013

Experimental Dermatology

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Psoriatic individuals demonstrate accelerated healing and the Koebner phenomenon, suggesting that psoriatic proliferation of keratinocytes is not inhibited appropriately after skin injury. Serial analysis of gene expression in TNFa-exposed keratinocytes shows the greatest alteration in expression of NMDA-R2C. Expression of the NMDA receptor is altered in diseased skin containing TNFa, and TNFa plays a prominent role in psoriasis. An abnormality in induction of NMDA-R2C by TNFa in psoriatic keratinocytes may explain their lack of growth inhibition. We compared the capacity of TNFa to induce expression of NMDA-R2C in normal and psoriatic (involved and uninvolved) keratinocytes in vitro. After 72 h of incubation with TNFa, normal keratinocytes demonstrated a significant induction of NMDA-R2C mRNA compared with control cultures, whereas psoriatic keratinocytes showed no induction. In an in vitro model of wounding (scratches on monolayers), TNFa inhibited migration/ proliferation of keratinocytes only at the edge of NMDA-R2C expressing wounded monolayers of normal keratinocytes.

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N‐methyl‐D‐aspartate receptors influence the intracellular calcium concentration of keratinocytes

Cited by 31 publications

References 35 publications

The Expression of NMDA Receptor 1 Correlates with Clinicopathological Parameters in Cutaneous Squamous Cell Carcinoma

The Expression of NMDA Receptor 1 Correlates with Clinicopathological Parameters in Cutaneous Squamous Cell Carcinoma

Transdermal delivery of xenon from lipophilic solution and water

Psoriatic keratinocytes are resistant to tumor necrosis factor alpha's induction of mRNA for the NMDA‐R2C subunit

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