title: Involvement of TACE/ADAM17 and ADAM10 in etoposide-induced apoptosis of germ cells in rat spermatogenesis.
abstract: Germ cell apoptosis is important to regulate sperm production in the mammalian testis, but the molecular mechanisms underlying apoptosis are still poorly understood. We have recently shown that in vitro, etoposide induces upregulation of TACE/ADAM17 and ADAM10, two membrane-bound extracellular metalloproteases. Here we show that in vivo these enzymes are involved in etoposide-, but not in heat shock-, induced apoptosis in rat spermatogenesis. Germ cell apoptosis induced by DNA damage was associated with an increase in protein levels and cell surface localization of TACE/ADAM17 and ADAM10. On the contrary, apoptosis of germ cells induced by heat stress, another cell death stimulus, did not change levels or localization of these proteins. Pharmacological in vivo inhibition of TACE/ADAM17 and ADAM10 prevents etoposide-induced germ cell apoptosis. Finally, Gleevec (STI571) a pharmacological inhibitor of p73, a master gene controlling apoptosis induced by etoposide, prevented the increase of TACE/ADAM17 levels. Our results strongly suggest that TACE/ADAM17 participates in in vivo apoptosis of male germ cells induced by DNA damage.
authors.affiliation: Departamento de Ciencias Fisiológicas, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Chile.
authors.forename: Carlos
authors.initials: C
authors.lastname: Lizama
authors.forename: Diego
authors.initials: D
authors.lastname: Rojas-Benitez
authors.forename: Marcelo
authors.initials: M
authors.lastname: Antonelli
authors.forename: Andreas
authors.initials: A
authors.lastname: Ludwig
authors.forename: Ricardo D
authors.initials: RD
authors.lastname: Moreno
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000072197:ADAM10 Protein; D000072198:ADAM17 Protein; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D004249:DNA Damage; D005047:Etoposide / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005854:Germ Cells / Q000187:drug effects*; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013091:Spermatogenesis / Q000187:drug effects*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C542371:ADAM10 protein, rat; D000072198:ADAM17 Protein; C000606464:Adam17 protein, rat