RESUMEN
Exposure to inorganic arsenic in contaminated drinking water poses an environmental public health threat for hundreds of millions of people in the US and around the world. Arsenic is a known carcinogen for skin cancer. However, the mechanism by which arsenic induces skin cancer remains poorly understood. Here, we have shown that arsenic induces p62 expression in an autophagy-independent manner in human HaCaT keratinocytes. In mouse skin, chronic arsenic exposure through drinking water increases p62 protein levels in the epidermis. Nrf2 is required for basal and arsenic-induced p62 up-regulation. p62 knockdown reduces arsenic-induced Nrf2 activity, and induces sustained p21 up-regulation. p62 induction is associated with increased proliferation in mouse epidermis. p62 knockdown had little effect on arsenic-induced apoptosis, while it decreased cell proliferation following arsenic treatment. Our findings indicate that arsenic induces p62 expression to regulate the Nrf2 pathway in human keratinocytes and suggest that targeting p62 may help prevent arsenic-induced skin cancer.
Asunto(s)
Arsénico/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Proteína Sequestosoma-1/genética , Animales , Arsénico/efectos adversos , Autofagia/efectos de los fármacos , Autofagia/genética , Proliferación Celular/efectos de los fármacos , Transformación Celular Neoplásica/inducido químicamente , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Modelos Animales de Enfermedad , Técnicas de Silenciamiento del Gen , Humanos , Masculino , Ratones , Unión Proteica , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteína Sequestosoma-1/metabolismo , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/prevención & controlRESUMEN
OBJECTIVE: Ashwagandha, an Indian Ayurvedic medicine is indicated to prevent COVID-19 infection. Because IL-6 and C-reactive protein are widely measured to determine risk of cytokine storm in hospitalized COVID-19 patients, we studied potential interference of ashwagandha on these two assays. Previous studies indicated that ashwagandha may interfere with digoxin assay, so we also studied potential interference with digoxin assay. MATERIALS AND METHODS: We obtained one ashwagandha product from India (liquid extract) and one product from US (Herb Pharma; liquid extract). We prepared two serum pool each for IL-6, C-reactive protein and digoxin by combining appropriate left-over specimens submitted to our hospital laboratory for such tests. Then aliquots of each pools were supplemented with 10, 25 or 50 µL of ashwagandha extract followed by re-analysis for appropriate analyte and comparing values with original pool. RESULTS: We observed negative interference of ashwagandha with IL-6 assay only (Indian product showed more negative interference) but C-reactive protein assay and digoxin assay were not affected. Negative interference of ashwagandha in IL-6 assay has not been reported before. CONCLUSION: We conclude ashwagandha caused negative interference in IL-6 assay.