scholarly journals Arsenic leads to autophagy of keratinocytes by increasing aquaporin 3 expression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sebastian Yu ◽  
Ling-Hau Li ◽  
Chih-Hung Lee ◽  
Palaniraja Jeyakannu ◽  
Jeh-Jeng Wang ◽  
...  
Keyword(s):  
Rna Interference ◽  
Skin Cancer ◽  
Human Keratinocytes ◽  
Epidermal Keratinocytes ◽  
Quantitative Real Time Pcr ◽  
Membrane Channel ◽  
Primary Human Keratinocytes ◽  
Arsenic Uptake ◽  
Aquaporin 3 ◽  
Skin Cancers

AbstractExposure to arsenic, a ubiquitous metalloid on Earth, results in human cancers. Skin cancer is the most common arsenical cancers. Both autophagy and aquaporin pathway are known to promote carcinogenesis. However, the mechanisms by which arsenic regulates aquaporin and autophagy in arsenical skin cancers remain elusive. This study aims to address how arsenic regulates aquaporin-3, the predominant aquaporin in epidermal keratinocytes, and how this process would induce autophagy. Quantitative real-time PCR and immunofluorescence were used to measure the expression of aquaporin 3 in arsenical skin cancers and arsenic-treated keratinocytes. Beclin-1 expression and autophagy were measured. We examined if blocking aquaporin 3 could interfere arsenic-induced autophagy in keratinocytes. Expression of aquaporin 3 is increased in arsenical cancers and in arsenic-treated keratinocytes. Arsenic induced autophagy in primary human keratinocytes. Notably, the arsenic-induced autophagy was inhibited by pretreatment of keratinocytes with aquaporin inhibitors Auphen or AgNO3, or RNA interference against aquaporin 3. The data indicates that the aquaporin 3 is an important cell membrane channel to mediate arsenic uptake and contributes to the arsenic-induced autophagy.

scholarly journals β1 Integrins Regulate Keratinocyte Adhesion and Differentiation by Distinct Mechanisms

2000 ◽  
Vol 11 (2) ◽  
pp. 453-466 ◽  
Author(s):  
Laurence Levy ◽  
Simon Broad ◽  
Dagmar Diekmann ◽  
Richard D. Evans ◽  
Fiona M. Watt
Keyword(s):  
Point Mutations ◽  
Terminal Differentiation ◽  
Focal Adhesions ◽  
Human Keratinocytes ◽  
Proximal Part ◽  
Epidermal Keratinocytes ◽  
Β1 Integrin ◽  
Primary Human Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
Β1 Integrins

In keratinocytes, the β1 integrins mediate adhesion to the extracellular matrix and also regulate the initiation of terminal differentiation. To explore the relationship between these functions, we stably infected primary human epidermal keratinocytes and an undifferentiated squamous cell carcinoma line, SCC4, with retroviruses encoding wild-type and mutant chick β1 integrin subunits. We examined the ability of adhesion-blocking chick β1-specific antibodies to inhibit suspension-induced terminal differentiation of primary human keratinocytes and the ability of the chick β1 subunit to promote spontaneous differentiation of SCC4. A D154A point mutant clustered in focal adhesions but was inactive in the differentiation assays, showing that differentiation regulation required a functional ligand-binding domain. The signal transduced by β1 integrins in normal keratinocytes was “do not differentiate” (transduced by ligand-occupied receptors) as opposed to “do differentiate” (transduced by unoccupied receptors), and the signal depended on the absolute number, rather than on the proportion, of occupied receptors. Single and double point mutations in cyto-2 and -3, the NPXY motifs, prevented focal adhesion targeting without inhibiting differentiation control. However, deletions in the proximal part of the cytoplasmic domain, affecting cyto-1, abolished the differentiation-regulatory ability of the β1 subunit. We conclude that distinct signaling pathways are involved in β1 integrin–mediated adhesion and differentiation control in keratinocytes.

scholarly journals The Role of p53 in Progression of Cutaneous Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4507
Author(s):  
Minna Piipponen ◽  
Pilvi Riihilä ◽  
Liisa Nissinen ◽  
Veli-Matti Kähäri
Keyword(s):  
Squamous Cell Carcinoma ◽  
Skin Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tp53 Gene ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Epidermal Keratinocytes ◽  
Early Event ◽  
Skin Cancers

Skin cancers are the most common types of cancer worldwide, and their incidence is increasing. Melanoma, basal cell carcinoma (BCC), and cutaneous squamous cell carcinoma (cSCC) are the three major types of skin cancer. Melanoma originates from melanocytes, whereas BCC and cSCC originate from epidermal keratinocytes and are therefore called keratinocyte carcinomas. Chronic exposure to ultraviolet radiation (UVR) is a common risk factor for skin cancers, but they differ with respect to oncogenic mutational profiles and alterations in cellular signaling pathways. cSCC is the most common metastatic skin cancer, and it is associated with poor prognosis in the advanced stage. An important early event in cSCC development is mutation of the TP53 gene and inactivation of the tumor suppressor function of the tumor protein 53 gene (TP53) in epidermal keratinocytes, which then leads to accumulation of additional oncogenic mutations. Additional genomic and proteomic alterations are required for the progression of premalignant lesion, actinic keratosis, to invasive and metastatic cSCC. Recently, the role of p53 in the invasion of cSCC has also been elucidated. In this review, the role of p53 in the progression of cSCC and as potential new therapeutic target for cSCC will be discussed.

scholarly journals The E6 and E7 Proteins of the Cutaneous Human Papillomavirus Type 38 Display Transforming Properties

2003 ◽  
Vol 77 (3) ◽  
pp. 2195-2206 ◽  
Author(s):  
Sandra Caldeira ◽  
Ingeborg Zehbe ◽  
Rosita Accardi ◽  
Ilaria Malanchi ◽  
Wen Dong ◽  
...  
Keyword(s):  
Human Keratinocytes ◽  
Human Papillomaviruses ◽  
Host Cells ◽  
Primary Human Keratinocytes ◽  
Transition Control ◽  
Skin Cancers ◽  
E6 And E7 ◽  
E7 Proteins ◽  
Nonmelanoma Skin Cancers

ABSTRACT Several studies have suggested the involvement of cutaneous human papillomaviruses (HPVs) in the development of nonmelanoma skin cancers. Here we have characterized the in vitro properties of E7 proteins of three cutaneous HPV types, 10, 20, and 38, which are frequently detected in skin specimens. We show that HPV38 E7 is able to inactivate the tumor suppressor pRb and induces loss of G1/S transition control, a key event in carcinogenesis. In contrast, HPV10 and HPV20 E7 proteins do not display these in vitro transforming activities. We also show that the two early proteins E6 and E7 of HPV38 are sufficient to corrupt the cell cycle and senescence programs in primary cells, inducing active and long-lasting proliferation of primary human keratinocytes, the natural host cells. Our study shows that E6 and E7 of this cutaneous HPV type have transforming activity in primary human cells, suggesting a role for HPV38 infection in skin carcinogenesis. In further support of such a role, we detected HPV38 DNA in approximately 50% of nonmelanoma skin cancers, but only in 10% of healthy skin specimens (P < 0.001).

scholarly journals Lactobacillus rhamnosus GG Inhibits the Toxic Effects of Staphylococcus aureus on Epidermal Keratinocytes

2014 ◽  
Vol 80 (18) ◽  
pp. 5773-5781 ◽  
Author(s):  
Walaa Mohammedsaeed ◽  
Andrew J. McBain ◽  
Sheena M. Cruickshank ◽  
Catherine A. O'Neill
Keyword(s):  
Staphylococcus Aureus ◽  
Lactobacillus Rhamnosus ◽  
Culture Fluid ◽  
Human Keratinocytes ◽  
Probiotic Bacterium ◽  
Epidermal Keratinocytes ◽  
Protective Effects ◽  
Primary Human Keratinocytes ◽  
Content Type ◽  
Viable Bacteria

ABSTRACTFew studies have evaluated the potential benefits of the topical application of probiotic bacteria or material derived from them. We have investigated whether a probiotic bacterium,Lactobacillus rhamnosusGG, can inhibitStaphylococcus aureusinfection of human primary keratinocytes in culture. When primary human keratinocytes were exposed toS. aureus, only 25% of the keratinocytes remained viable following 24 h of incubation. However, in the presence of 108CFU/ml of liveL. rhamnosusGG, the viability of the infected keratinocytes increased to 57% (P= 0.01).L. rhamnosusGG lysates and spent culture fluid also provided significant protection to keratinocytes, with 65% (P= 0.006) and 57% (P= 0.01) of cells, respectively, being viable following 24 h of incubation. Keratinocyte survival was significantly enhanced regardless of whether the probiotic was applied in the viable form or as cell lysates 2 h before or simultaneously with (P= 0.005) or 12 h after (P= 0.01)S. aureusinfection. However, spent culture fluid was protective only if added before or simultaneously withS. aureus. With respect to mechanism, bothL. rhamnosusGG lysate and spent culture fluid apparently inhibited adherence ofS. aureusto keratinocytes by competitive exclusion, but only viable bacteria or the lysate could displaceS. aureus(P= 0.04 and 0.01, respectively). Furthermore, growth ofS. aureuswas inhibited by either live bacteria or lysate but not spent culture fluid. Together, these data suggest at least two separate activities involved in the protective effects ofL. rhamnosusGG againstS. aureus, growth inhibition and reduction of bacterial adhesion.

scholarly journals Downregulation of 14-3-3σ Prevents Clonal Evolution and Leads to Immortalization of Primary Human Keratinocytes

2000 ◽  
Vol 149 (5) ◽  
pp. 1117-1130 ◽  
Author(s):  
Elena Dellambra ◽  
Osvaldo Golisano ◽  
Sergio Bondanza ◽  
Emanuela Siviero ◽  
Pedro Lacal ◽  
...  
Keyword(s):  
Replicative Senescence ◽  
Clonal Evolution ◽  
Human Keratinocytes ◽  
Telomerase Activity ◽  
Suppressor Gene ◽  
Epidermal Keratinocytes ◽  
Primary Human Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
Continuous Transition ◽  
Endogenous Gene

In human epidermal keratinocytes, replicative senescence, is determined by a progressive decline of clonogenic and dividing cells. Its timing is controlled by clonal evolution, that is, by the continuous transition from stem cells to transient amplifying cells. We now report that downregulation of 14-3-3σ, which is specifically expressed in human stratified epithelia, prevents keratinocyte clonal evolution, thereby forcing keratinocytes into the stem cell compartment. This allows primary human keratinocytes to readily escape replicative senescence. 14-3-3σ–dependent bypass of senescence is accompanied by maintenance of telomerase activity and by downregulation of the p16INK4a tumor suppressor gene, hallmarks of keratinocyte immortalization. Taken together, these data therefore suggest that inhibition of a single endogenous gene product fosters immortalization of primary human epithelial cells without the need of exogenous oncogenes and/or oncoviruses.

Alterations of ultrastructure and elemental composition in cultured human epidermal keratinocytes after treatment with nitrofurazone and silver sulfadiazine

1987 ◽  
Vol 45 ◽  
pp. 676-677
Author(s):  
A. R. Crooker ◽  
M. C. Myers ◽  
T. L. Beard ◽  
E. S. Graham
Keyword(s):  
Electron Microscopy ◽  
Elemental Composition ◽  
Pyrolytic Carbon ◽  
Human Keratinocytes ◽  
Silver Sulfadiazine ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
Culture Systems ◽  
Cytotoxicity Endpoints

Cell culture systems have become increasingly popular as a means of screening toxic agents and studying toxic mechanisms of drugs and other chemicals at the cellular and subcellular levels. These in vitro tests can be conducted rapidly in a broad range of relevant mammalian culture systems; a variety of biological and biochemical cytotoxicity endpoints can be examined. The following study utilized human keratinocytes to evaluate the relative cytotoxicities of nitrofurazone (NF) and silver sulfadiazine (SS), the active ingredients of FURACIN(R) Topical Cream and SILVADENE(R) Cream, respectively. These compounds are anti-infectives used in the treatment of burn patients. Cell ultrastructure and elemental composition were utilized as cytotoxicity endpoints.Normal Human Epidermal Keratinocytes (HK) were prepared from the EpiPackTM culture system (Clonetics Corporation, Boulder, CO). For scanning electron microscopy (SEM) and transmission electron microscopy (TEM), cells were seeded on sterile 35 mm Falcon plastic dishes; for elemental microanalysis, cells were plated on polished pyrolytic carbon discs (E. Fullam, Latham, NY) placed in the culture dishes.

Novel Nanolipoidal Systems for the Management of Skin Cancer

2020 ◽  
Vol 14 (2) ◽  
pp. 108-125
Author(s):  
Apoorva Singh ◽  
Nimisha
Keyword(s):  
Skin Cancer ◽  
Survival Rates ◽  
Cancer Therapeutics ◽  
The Body ◽  
Surgical Removal ◽  
The Novel ◽  
Skin Cancers ◽  
Recent Developments ◽  
Abnormal Cells ◽  
The Stability

: Skin cancer, among the various kinds of cancers, is a type that emerges from skin due to the growth of abnormal cells. These cells are capable of spreading and invading the other parts of the body. The occurrence of non-melanoma and melanoma, which are the major types of skin cancers, has increased over the past decades. Exposure to ultraviolet radiations (UV) is the main associative cause of skin cancer. UV exposure can inactivate tumor suppressor genes while activating various oncogenes. The conventional techniques like surgical removal, chemotherapy and radiation therapy lack the potential for targeting cancer cells and harm the normal cells. However, the novel therapeutics show promising improvements in the effectiveness of treatment, survival rates and better quality of life for patients. Different methodologies are involved in the skin cancer therapeutics for delivering the active ingredients to the target sites. Nano carriers are very efficient as they have the ability to improve the stability of drugs and further enhance their penetration into the tumor cells. The recent developments and research in nanotechnology have entitled several targeting and therapeutic agents to be incorporated into nanoparticles for an enhancive treatment of skin cancer. To protect the research works in the field of nanolipoidal systems various patents have been introduced. Some of the patents acknowledge responsive liposomes for specific targeting, nanocarriers for the delivery or co-delivery of chemotherapeutics, nucleic acids as well as photosensitizers. Further recent patents on the novel delivery systems have also been included here.

scholarly journals Systemic Photoprotection in Skin Cancer Prevention: Knowledge among Dermatologists

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 332
Author(s):  
Luca Fania ◽  
Francesca Sampogna ◽  
Francesco Ricci ◽  
Mariafrancesca Hyeraci ◽  
Andrea Paradisi ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Sampling Procedure ◽  
Skin Cancer Prevention ◽  
Snowball Sampling ◽  
Scientific Publications ◽  
Current State ◽  
Skin Cancers ◽  
Knowledge And Attitude ◽  
Nonmelanoma Skin Cancers

Background: Systemic photoprotection (i.e., administration of substances such as nicotinamide, carotenoids, and vitamin D) may be important to reduce photocarcinogenesis or to support long-term protection against UV irradiation. Clinical trials showed that oral nicotinamide is effective in reducing the onset of new nonmelanoma skin cancers (NMSCs), while other oral photoprotectors failed to achieve the reduction of new melanoma or NMSC formation in humans. The aim of this study was to summarize the current state of knowledge of systemic photoprotection and to evaluate the knowledge and attitude of dermatologists regarding these treatments. Methods: The survey was conducted on a sample of dermatologists recruited according to a snowball sampling procedure. The questionnaire consisted of a first part asking for characteristics of the participant and a second part with 12 specific questions on their knowledge about systemic photoprotection, particularly their knowledge of astaxanthin, β-carotene, nicotinamide, and vitamin D3. Results: One hundred eight dermatologists answered the survey. Most of them (85.2%) stated that oral photoprotectors have a role in the prevention of skin cancer, and responses mainly mentioned nicotinamide. More than half of them (54.6%) had prescribed all the considered oral photoprotectors, but the majority of them had prescribed nicotinamide, mainly for 2 to 3 months during summer, almost invariably (n = 106) associated with topical photoprotectors. Most dermatologists (>80%) were aware of scientific publications demonstrating an effect of systemic photoprotectors on NMSC. Conclusions: Most Italian dermatologists have positive views on oral photoprotection in skin cancer and are aware of the demonstrated potential of nicotinamide in the prevention of NMSCs.

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