UVB-Stimulated TNFα Release from Human Melanocyte and Melanoma Cells Is Mediated by p38 MAPK

Muthusamy, Visalini; Piva, Terrence J.

doi:10.3390/ijms140817029

Cited by 8 publications

(12 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[28][29][30][31] Therefore, in addition to the B-Raf/ERK pathway, the activation of NF-jB or inactivation of AP-1 may play a role in melanoma development. 21,25 Our study identified significantly increased levels of phosphorylated ERK and JNK after exposure to both UVA and UVB. The phosphorylation persisted for a longer time with UVA.…”

Section: Discussionmentioning

confidence: 69%

“…Furthermore, only a few investigations have compared the effects of different wavelengths. In melanocytes and melanoma, UV has been shown to induce phosphorylation of the p38 and JNK/stress‐activated protein kinase pathways, whereas NF‐κB remains at constantly high expression . The B‐Raf/ERK pathway has been suggested as the central pathway involved in melanoma development and progression.…”

Section: Discussionmentioning

confidence: 99%

“…In melanocytes and melanoma, UV has been shown to induce phosphorylation of the p38 and JNK/stress-activated protein kinase pathways, whereas NF-jB remains at constantly high expression. [19][20][21][22][23][24] The B-Raf/ ERK pathway has been suggested as the central pathway involved in melanoma development and progression. However, advances in the understanding of the signalling pathways in melanoma have identified altered expression of especially NF-jB, and also AP-1, among others, to promote tumour development.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Cell fate regulated by nuclear factor‐κB‐ and activator protein‐1‐dependent signalling in human melanocytes exposed to ultraviolet A and ultraviolet B

2014

View full text Add to dashboard Cite

SummaryBackgroundUltraviolet (UV) radiation constitutes an important risk factor for malignant melanoma, but the wavelength responsible for the initiation of this disease is not fully elucidated. Solar UV induces multiple signalling pathways that are critical for initiation of apoptotic cell death as a cellular defence against malignant transformation.ObjectivesTo evaluate the involvement of the transcription factors nuclear factor (NF)-κB and activator protein (AP)-1 in the signalling pathways induced by UVA or UVB irradiation in human melanocytes.MethodsPrimary cultures of normal human melanocytes were irradiated with UVA or UVB, and the concomitant DNA damage and redox alterations were monitored. The resulting activation of the NF-κB and AP-1 signalling pathways and subsequent apoptosis were studied.ResultsUVB irradiation causes DNA damage detected as formation of cyclobutane pyrimidine dimers, while UVA induces increased levels of 8-hydroxydeoxyguanosine and lipid peroxidation. UVA and UVB initiate phosphorylation of c-Jun N-terminal protein kinase and extracellular signal-regulated kinase, and the apoptosis signalling pathways converge into a common mechanism. Downregulation of c-Jun suppresses AP-1-mediated signalling and prevents apoptosis upstream of lysosomal and mitochondrial membrane permeabilization, whereas inhibition of NF-κB by SN50 increases apoptosis.ConclusionsWe conclude that AP-1 induces proapoptotic signalling, whereas NF-κB is a key antiapoptotic/prosurvival factor in both UVA- and UVB-induced cellular damage in human melanocytes, which might in turn impact melanoma development and progression.What's already known about this topic? Melanocytes are the target cells of ultraviolet (UV) irradiation, and the cells from which melanoma originates. The mitogen-activated protein kinase signalling pathway is important for regulation of UV-induced cellular responses. Previous studies have strongly implicated the transcription factors activator protein (AP)-1 and nuclear factor (NF)-κB as mediators of the UV response in other cell types. What does this study add? The present study identifies NF-κB as an antiapoptotic/prosurvival factor and shows that AP-1 stimulates proapoptotic signalling during both UVA- and UVB-induced apoptosis in human melanocytes. An improved understanding of cellular responses in UV-exposed melanocytes is essential to understanding and preventing the formation of melanoma, and might provide an opportunity to identify apoptotic regulators.

show abstract

Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cell fate regulated by nuclear factor‐κB‐ and activator protein‐1‐dependent signalling in human melanocytes exposed to ultraviolet A and ultraviolet B

2014

View full text Add to dashboard Cite

show abstract

“…López et al, reported that paracrine protective effects of CM from UVB-irradiated KC on MC involved regulation of various signaling pathways including proinflammatory and p53-dependent apoptotic pathways [42]. Our study demonstrated that the microenvironment created by KC reversed damaging effects of UVB on MC by reducing activation of caspase-3 and p53 that play a crucial role in UVR-mediated apoptosis associated with DNA damage [25,26], and by downregulating inflammatory markers including NF-κB activation and TNF-α levels implicated in photodamaged skin [46,47]. Nevertheless, depletion of Nrf2 in KC resulted in suppression of its protective effects on UVB-mediated DNA damage, apoptosis and inflammatory response in MC.…”

Section: Discussionmentioning

confidence: 93%

Nrf2 in keratinocytes modulates UVB-induced DNA damage and apoptosis in melanocytes through MAPK signaling

Jeayeng

Wongkajornsilp

Slominski

et al. 2017

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Responses of melanocytes (MC) to ultraviolet (UV) irradiation can be influenced by their neighbouring keratinocytes (KC). We investigated the role of Nrf2 in regulating paracrine effects of KC on UVB-induced MC responses through phosphorylation of MAPKs in association with oxidative stress in primary human MC cocultured with primary human KC using a transwell co-culture system and small-interfering RNA-mediated silencing of Nrf2 (siNrf2). The mechanisms by which Nrf2 modulated paracrine factors including α-melanocyte-stimulating hormone (α-MSH) and paracrine effects of KC on UVB-mediated apoptosis were also assessed. Our findings showed that co-culture of MC with siNrf2-transfected KC enhanced UVB-mediated cyclobutane pyrimidine dimer (CPD) formation, apoptosis and oxidant formation, together with phosphorylation of ERK, JNK and p38 in MC. Treatment of MC with conditioned medium (CM) from Nrf2-depleted KC also increased UVB-mediated MC damage, suggesting that KC modulated UVB-mediated MC responses via paracrine effects. Additionally, depletion of Nrf2 in KC suppressed UVB-induced α-MSH levels as early as 30 min post-irradiation, although pretreatment with N-acetylcysteine (NAC) elevated its levels in CM from siNrf2-transfected KC. Furthermore, NAC reversed the effect of CM from Nrf2-depleted KC on UVB-induced apoptosis and inflammatory response in MC. Our study demonstrates for the first time that KC provided a rescue effect on UVB-mediated MC damage, although depletion of Nrf2 in KC reversed its protective effects on MC in a paracrine fashion in association with elevation of ROS levels and activation of MAPK pathways in MC. Nrf2 may indirectly regulate the paracrine effects of KC probably by affecting levels of the paracrine factor α-MSH via a ROS-dependent mechanism.

show abstract

“…The algal extract introduced at a final content of 5% (w/w) allowed significant anti UV-B activity. UV radiation induces diverse effects for human skin like sunburn, inflammation, alteration of cytokine levels in cells found in the epidermis and dermis, and causes skin aging by the reaction of free radicals and reactive oxygen species and/or formation of aggressive malignant skin cancer (Muthusamy and Piva 2013). The UV-B-induced pyrimidine dimers in DNA can lead to a form of programmed apoptosis or can cause DNA replication errors.…”

Section: Detection Of Palythenic Acidmentioning

confidence: 99%

Chemical characterization and photoprotective activity measurement of extracts from the red macroalga Solieria chordalis

et al. 2014

View full text Add to dashboard Cite

International audienceThe photoadaptive responses of macroalgal communities to abiotic stresses have been studied, and a number of UV-absorbing molecules have been identified. Among these compounds, photoprotective compounds such as mycosporine-like amino acids and carotenoids have been isolated from various red macroalgal species. However, several substances still need to be characterized. We describe the preparation of photoprotective extracts obtained from Solieria chordalis. Two solvents, 2-octyl dodecanol and octyldodecyl ester of L-pyrrolidone carboxylic acid, were selected based on their cosmetic functions for performing an ultrasound-assisted extraction. The efficiency of extraction was monitored by spectrophotometry and in vitro photoprotective activity measurements. 2-Octyl dodecanol and octyldodecyl ester of L-pyrrolidone carboxylic acid extracts showed maximum absorption wavelengths ranging from 280 to 340 nm and 270 to 350 nm, respectively. The anti UV-B capacity for protecting a synthetic chlorophyll solution was assessed by measuring its pseudo first-order degradation kinetics at room temperature. Under irradiation at 312 nm, chlorophyll introduced in the 2-octyl dodecanol S. chordalis extract showed the slowest degradation kinetics with a half-life t(1/2) of 121.0 min. Several compounds were detected in the seawee

show abstract

UVB-Stimulated TNFα Release from Human Melanocyte and Melanoma Cells Is Mediated by p38 MAPK

Cited by 8 publications

References 56 publications

Cell fate regulated by nuclear factor‐κB‐ and activator protein‐1‐dependent signalling in human melanocytes exposed to ultraviolet A and ultraviolet B

Cell fate regulated by nuclear factor‐κB‐ and activator protein‐1‐dependent signalling in human melanocytes exposed to ultraviolet A and ultraviolet B

Nrf2 in keratinocytes modulates UVB-induced DNA damage and apoptosis in melanocytes through MAPK signaling

Chemical characterization and photoprotective activity measurement of extracts from the red macroalga Solieria chordalis

Contact Info

Product

Resources

About