{"id":2651,"date":"2002-08-05T10:20:15","date_gmt":"2002-08-05T08:20:15","guid":{"rendered":"http:\/\/www.isidorolab.com\/public\/?p=2651"},"modified":"2021-09-05T10:24:54","modified_gmt":"2021-09-05T08:24:54","slug":"endosomal-lysosomal-proteolysis-mediates-death-signalling-by-tnfalpha-not-by-etoposide-in-l929-fibrosarcoma-cells-evidence-for-an-active-role-of-cathepsin-d","status":"publish","type":"post","link":"http:\/\/www.isidorolab.com\/public\/index.php\/2002\/08\/05\/endosomal-lysosomal-proteolysis-mediates-death-signalling-by-tnfalpha-not-by-etoposide-in-l929-fibrosarcoma-cells-evidence-for-an-active-role-of-cathepsin-d\/","title":{"rendered":"Endosomal-lysosomal proteolysis mediates death signalling by TNFalpha, not by etoposide, in L929 fibrosarcoma cells: evidence for an active role of cathepsin D"},"content":{"rendered":"\t\t<div data-elementor-type=\"wp-post\" data-elementor-id=\"2651\" class=\"elementor elementor-2651\">\n\t\t\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-2ee137e5 elementor-section-stretched elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"2ee137e5\" data-element_type=\"section\" data-settings=\"{&quot;stretch_section&quot;:&quot;section-stretched&quot;}\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-274bac1a\" data-id=\"274bac1a\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-65e1207a elementor-widget elementor-widget-text-editor\" data-id=\"65e1207a\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t\t\t\t\t\t\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=D%C3%A9moz+M&amp;cauthor_id=12437111\">Marina D\u00e9moz<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/12437111\/#affiliation-1\"> 1 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Castino+R&amp;cauthor_id=12437111\">Roberta Castino<\/a>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Cesaro+P&amp;cauthor_id=12437111\">Patrizia Cesaro<\/a>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Baccino+FM&amp;cauthor_id=12437111\">Francesco M Baccino<\/a>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Bonelli+G&amp;cauthor_id=12437111\">Gabriella Bonelli<\/a>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Isidoro+C&amp;cauthor_id=12437111\">Ciro Isidoro<\/a><\/p>\n<p>\u00a0<\/p>\n\n<h3 class=\"wp-block-heading\">Affiliation<\/h3>\n\n<p><sup>1<\/sup> Dipartimento di Scienze Mediche, Universit\u00e0 A Avogadro, Novara, Italy.<\/p>\n\n<p>PMID: <strong>12437111<\/strong><\/p>\n<p>DOI: <a href=\"https:\/\/doi.org\/10.1515\/bc.2002.137\" target=\"_blank\" rel=\"noreferrer noopener\">10.1515\/BC.2002.137<\/a><\/p>\n\n<p>Biol Chem. Jul-Aug 2002;383(7-8):1237-48. doi: 10.1515\/BC.2002.137.<\/p>\n<p>\u00a0<\/p>\n<hr \/>\n<h2 class=\"wp-block-heading\">Abstract<\/h2>\n\n<p>In several &#8216;in vitro&#8217; models of apoptosis, lysosomal proteolysis has been shown to play an active role in mediating the death signal by cytokines or antiblastic drugs. Depending on the experimental cell model and the cytotoxic stimulus applied, an increased expression and the cytosolic translocation of either cathepsin D or B have been reported in apoptotic cells. We have analysed the involvement of these lysosomal proteases in a canonical apoptotic cell model, namely L929 fibroblasts, in which apoptosis was induced by cytotoxic agents acting through different mechanisms: (i) the cytokine TNFalpha, which triggers the cell suicide via interaction with its membrane receptor, and (ii) the topoisomerase II-inhibitor etoposide (VP16), which directly causes DNA damage. In both cases the activity of cathepsins B and D increased in apoptosing cultures. CA074-Me, a specific inhibitor of cathepsin B, and Leupeptin, a broad inhibitor of serine and cysteine proteases (among which is cathepsin B), did not exert any protection from TNFalpha. In contrast, pre-loading the cells with pepstatin A, a specific inhibitor of cathepsin D, protected L929 cells from TNFalpha cytotoxicity by more than 50%. However, no protection was observed if pepstatin A was added concomitantly with the cytokine. Inhibition of either cathepsin B or D did not impede apoptosis induced by etoposide. Lysosomal integrity was preserved and cathepsin D remained still confined in vesicular structures in apoptotic cells treated with either TNFalpha or etoposide. It follows that proteolysis by cathepsin D is likely to represent an early event in the death pathway triggered by TNFalpha and occurs within the endosomal-lysosomal compartment.<\/p>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<\/div>\n\t\t<div style='text-align:center' class='yasr-auto-insert-visitor'><!--Yasr Visitor Votes Shortcode--><div id='yasr_visitor_votes_0d4f6e04e90f9' class='yasr-visitor-votes'><div class=\"yasr-custom-text-vv-before yasr-custom-text-vv-before-2651\">Clicca per votare questo articolo!<\/div><div id='yasr-vv-second-row-container-0d4f6e04e90f9'\r\n                                        class='yasr-vv-second-row-container'><div id='yasr-visitor-votes-rater-0d4f6e04e90f9'\r\n                                      class='yasr-rater-stars-vv'\r\n                                      data-rater-postid='2651'\r\n                                      data-rating='0'\r\n                                      data-rater-starsize='32'\r\n                                      data-rater-readonly='false'\r\n                                      data-rater-nonce='bb8f69d06e'\r\n                                      data-issingular='false'\r\n                                    ><\/div><div class=\"yasr-vv-stats-text-container\" id=\"yasr-vv-stats-text-container-0d4f6e04e90f9\"><svg xmlns=\"https:\/\/www.w3.org\/2000\/svg\" width=\"20\" height=\"20\"\r\n                                   class=\"yasr-dashicons-visitor-stats\"\r\n                                   data-postid=\"2651\"\r\n                                   id=\"yasr-stats-dashicon-0d4f6e04e90f9\">\r\n                                   <path d=\"M18 18v-16h-4v16h4zM12 18v-11h-4v11h4zM6 18v-8h-4v8h4z\"><\/path>\r\n                               <\/svg><span id=\"yasr-vv-text-container-0d4f6e04e90f9\" class=\"yasr-vv-text-container\">[Total: <span id=\"yasr-vv-votes-number-container-0d4f6e04e90f9\">0<\/span>  Average: <span id=\"yasr-vv-average-container-0d4f6e04e90f9\">0<\/span>]<\/span><\/div><div id='yasr-vv-loader-0d4f6e04e90f9' class='yasr-vv-container-loader'><\/div><\/div><div id='yasr-vv-bottom-container-0d4f6e04e90f9' class='yasr-vv-bottom-container'><\/div><\/div><!--End Yasr Visitor Votes Shortcode--><\/div>","protected":false},"excerpt":{"rendered":"<p>Marina D\u00e9moz\u00a0 1 ,\u00a0Roberta Castino,\u00a0Patrizia Cesaro,\u00a0Francesco M Baccino,\u00a0Gabriella Bonelli,\u00a0Ciro Isidoro \u00a0 Affiliation 1 Dipartimento di Scienze Mediche, Universit\u00e0 A Avogadro, Novara, Italy. PMID: 12437111 DOI: 10.1515\/BC.2002.137 Biol Chem. Jul-Aug 2002;383(7-8):1237-48. doi: 10.1515\/BC.2002.137. \u00a0 Abstract In several &#8216;in vitro&#8217; models of apoptosis, lysosomal proteolysis has been shown to play an active role in mediating the death&hellip;<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"yasr_overall_rating":0,"yasr_post_is_review":"","yasr_auto_insert_disabled":"","yasr_review_type":"","footnotes":""},"categories":[136],"tags":[55],"class_list":["post-2651","post","type-post","status-publish","format-standard","hentry","category-paper","tag-cancer"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\r\n<title>Endosomal-lysosomal proteolysis mediates death signalling by TNFalpha, not by etoposide, in L929 fibrosarcoma cells: evidence for an active role of cathepsin D - IsidoroLab<\/title>\r\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\r\n<link rel=\"canonical\" href=\"http:\/\/www.isidorolab.com\/public\/index.php\/2002\/08\/05\/endosomal-lysosomal-proteolysis-mediates-death-signalling-by-tnfalpha-not-by-etoposide-in-l929-fibrosarcoma-cells-evidence-for-an-active-role-of-cathepsin-d\/\" \/>\r\n<meta property=\"og:locale\" content=\"it_IT\" \/>\r\n<meta property=\"og:type\" content=\"article\" \/>\r\n<meta property=\"og:title\" content=\"Endosomal-lysosomal proteolysis mediates death signalling by TNFalpha, not by etoposide, in L929 fibrosarcoma cells: evidence for an active role of cathepsin D - IsidoroLab\" \/>\r\n<meta property=\"og:description\" content=\"Marina D\u00e9moz\u00a0 1 ,\u00a0Roberta Castino,\u00a0Patrizia Cesaro,\u00a0Francesco M Baccino,\u00a0Gabriella Bonelli,\u00a0Ciro Isidoro \u00a0 Affiliation 1 Dipartimento di Scienze Mediche, Universit\u00e0 A Avogadro, Novara, Italy. 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