Pharmacological activation of TRPV4 produces immediate cell damage and induction of apoptosis in human melanoma cells and HaCaT keratinocytes
Publication Date
January 02, 2018
Authors
Aida Olivan Viguera, Angel Luis Garcia Otin, Javier Lozano Gerona, Edgar Abarca Lachen, et al
Volume
13
Issue
1
Pages
e0190307
DOI
https://dx.plos.org/10.1371/journal.pone.0190307
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0190307
Scopus
85039974946
Mendeley
http://www.mendeley.com/research/pharmacological-activation-trpv4-produces-immediate-cell-damage-induction-apoptosis-human-melanoma-c
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Mendeley | Further Information

{"title"=>"Pharmacological activation of TRPV4 produces immediate cell damage and induction of apoptosis in human melanoma cells and HaCaT keratinocytes", "type"=>"journal", "authors"=>[{"first_name"=>"Aida", "last_name"=>"Olivan-Viguera", "scopus_author_id"=>"55392319300"}, {"first_name"=>"Angel Luis", "last_name"=>"Garcia-Otin", "scopus_author_id"=>"6603484036"}, {"first_name"=>"Javier", "last_name"=>"Lozano-Gerona", "scopus_author_id"=>"57193227202"}, {"first_name"=>"Edgar", "last_name"=>"Abarca-Lachen", "scopus_author_id"=>"57056422300"}, {"first_name"=>"Ana J.", "last_name"=>"Garcia-Malinis", "scopus_author_id"=>"56458994700"}, {"first_name"=>"Kirk L.", "last_name"=>"Hamilton", "scopus_author_id"=>"56273577600"}, {"first_name"=>"Yolanda", "last_name"=>"Gilaberte", "scopus_author_id"=>"6602085309"}, {"first_name"=>"Esther", "last_name"=>"Pueyo", "scopus_author_id"=>"7004512193"}, {"first_name"=>"Ralf", "last_name"=>"Köhler", "scopus_author_id"=>"7201611491"}], "year"=>2018, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-85039974946", "pui"=>"620020628", "doi"=>"10.1371/journal.pone.0190307", "isbn"=>"1111111111", "sgr"=>"85039974946", "pmid"=>"29293584"}, "id"=>"b732400d-5b22-3276-baa9-379155cf1605", "abstract"=>"BACKGROUND: TRPV4 channels are calcium-permeable cation channels that are activated by several physicochemical stimuli. Accordingly, TRPV4 channels have been implicated in the regulation of osmosensing, mechanotransduction, thermosensation, and epithelial/endothelial barrier functions. Whether TRPV4 is also mechanistically implicated in melanoma cell proliferation is not clear. Here, we hypothesized that TRPV4 is expressed in human melanoma and that pharmacological activation interferes with cell proliferation. METHODOLOGY/PRINCIPAL FINDINGS: TRPV4 functions were studied in melanoma cell lines (A375, SK-MEL-28, MKTBR), immortalized non-cancer keratinocytes (HaCaT), and murine 3T3 fibroblasts by patch-clamp, qRT-PCR, intracellular calcium measurements, cell proliferation, and flow cytometric assays of apoptosis and cell cycle. The selective TRPV4-activator, GSK1016790A, elicited non-selective cation currents with TRPV4-typical current-voltage-relationship in all cell lines. GSK1016790A-induced currents were blocked by the TRPV4-blocker, HC067047. TRPV4 mRNA expression was demonstrated by qRT-PCR. In A375 cells, TRPV4 activation was frequently paralleled by co-activation of calcium/calmodulin-regulated KCa3.1 channels. Light microscopy showed that TRPV4-activation produced rapid cellular disarrangement, nuclear densification, and detachment of a large fraction of all melanoma cell lines and HaCaT cells. TRPV4-activation induced apoptosis and drastically inhibited A375 and HaCaT proliferation that could be partially prevented by HC067047. CONCLUSIONS/SIGNIFICANCE: Our study showed that TRPV4 channels were functionally expressed in human melanoma cell lines and in human keratinocytes. Pharmacological TRPV4 activation in human melanoma cells and keratinocytes caused severe cellular disarrangement, necrosis and apoptosis. Pharmacological targeting of TRPV4 could be an alternative or adjuvant therapeutic strategy to treat melanoma progression and other proliferative skin disorders.", "link"=>"http://www.mendeley.com/research/pharmacological-activation-trpv4-produces-immediate-cell-damage-induction-apoptosis-human-melanoma-c", "reader_count"=>8, "reader_count_by_academic_status"=>{"Unspecified"=>4, "Professor > Associate Professor"=>1, "Student > Ph. D. Student"=>1, "Student > Master"=>1, "Student > Postgraduate"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>4, "Professor > Associate Professor"=>1, "Student > Ph. D. Student"=>1, "Student > Master"=>1, "Student > Postgraduate"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>5, "Agricultural and Biological Sciences"=>2, "Medicine and Dentistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Unspecified"=>{"Unspecified"=>5}}, "group_count"=>0}

Scopus | Further Information

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