FLIP is expressed in mouse testis and protects germ cells from apoptosis

Alessio D'Alessio, C Giampietri, S Petrungaro, P Coluccia, D Starace, A Riccioli, F Padula, Sm Srinivasula, E Alnemri, F Palombi, A Filippini, E Ziparo, P. De Cesaris

Risultato della ricerca: Contributo in rivistaArticolo in rivista

31 Citazioni (Scopus)

Abstract

Apoptosis control in adult testis is crucial to achieve normal spermatogenesis. In this study c-FLIP, an apoptosis-modulating protein, was investigated. In Western blot and immunohistochemical analyses, the 55 KDa c-FLIP long isoform (c-FLIP(L)) was found to be expressed strongly in spermatocytes and spermatids, at low levels in spermatogonia and at almost undetectable levels in Sertoli cells. This expression pattern was confirmed by Northern blot analyses. Further experiments carried out on GC-1spg germ cell line revealed that reducing c-FLIP(L) expression increases Fas-dependent apoptosis. Conversely, restoring c-FLIP(L) expression reduces this response to control levels. Caspase-10 expression was found to match c-FLIP(L) expression pattern; further, caspase-10 activation upon anti-Fas treatment inversely correlated with c-FLIP(L) expression. Finally, TUNEL staining of seminiferous tubules incubated with anti-Fas antibody showed that apoptosis occurs mostly in basally located germ cells, indicating that such cells, expressing low levels of c-FLIP(L), are sensitive to Fas-mediated apoptosis. These data indicate for the first time that c-FLIP(L) might control germ cell apoptosis and caspase activity in the adult testis.
Lingua originaleEnglish
pagine (da-a)175-184
Numero di pagine10
RivistaCell Death and Differentiation
Volume10
DOI
Stato di pubblicazionePubblicato - 2003

Keywords

  • Animals
  • Antigens, CD95
  • Apoptosis
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • Caspases
  • Cells, Cultured
  • Enzyme Activation
  • Germ Cells
  • Male
  • Mice
  • Mice, Inbred Strains
  • Protein Isoforms
  • Seminiferous Tubules
  • Sertoli Cells
  • Spermatids
  • Spermatocytes
  • Spermatogonia
  • Testis

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