The immunomodulatory protein SV-IV protects serum-deprived cells against apoptosis but not against G0/G1 arrest: possible implications for the survival of implanting embryo.
Serum deprivation induced in human lymphoblastoid Raji cells oxidative stress-associated apoptotic death and G0/G1 cell cycle arrest. Addition into culture medium of the immunomodulatory protein Seminal vesicle protein 4 (SV-IV) protected these cells against apoptosis but not against cycle arrest. The antiapoptotic activity was related to: (1) decrease of endocellular reactive Oxygen species (ROS) (2) increase of mRNAs encoding anti-oxidant enzymes (catalase, G6PD) and antiapoptotic proteins (survivin, cox-1, Hsp70, c-Fos); (3) decrease of mRNAs encoding proapoptotic proteins (c-myc, Bax, caspase-3, Apaf-1). The biochemical changes underlaying these effects were probably induced by a protein tyrosine kinase (PTK) activity triggered by the binding of SV-IV to its putative plasma membrane receptors. The ineffectiveness of SV-IV to abrogate the cycle arrest was accounted for by its downregulating effects on D1,3/E G1-cyclins and CdK2/4 gene expression, ppRb/pRb ratio, and intracellular ROS concentration. In conclusion, these experiments: (1) prove that SV-IV acts as a cell survival factor; (2) suggest the involvement of a PTK in SV-IV signaling; (3) point to cell cycle-linked enzyme inhibition as responsible for cycle arrest; (4) provide a model to dissect the cycle arrest and apoptosis induced by serum withdrawal; (5) imply a possible role of SV-IV in the survival of hemiallogenic implanting embryos.
Morelli
Francesco
F
Institute of Genetics and Biophysics Adriano Buzzati-Traverso, CNR, Via P Castellino 111, Naples, Italy.
Peluso
Gianfranco
G
Petillo
Orsolina
O
Giannattasio
Angela
A
Filosa
Silvana
S
Motta
Chiara M
CM
Tammaro
Stefania
S
Zatterale
Adriana
A
Calzone
Rita
R
Budillon
Alfredo
A
Cartenì
Maria
M
de Maria
Salvatore
S
Costanza
Maria R
MR
Nigro
Antonella
A
Petrazzuolo
Marcella
M
Buommino
Elisabetta
E
Rizzo
Maria
M
Capasso
Giovanni
G
Baiano
Salvatore
S
Moscatiello
Francesco
F
Ravagnan
Gianpietro
G
Fuggetta
Maria P
MP
Tajana
Gianfranco
G
Stiuso
Paola
P
Metafora
Bianca M
BM
Metafora
Vittoria
V
Metafora
Salvatore
S
D000818:Animals; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016895:Culture Media, Serum-Free / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D053938:DNA Fragmentation; D046149:Embryo Culture Techniques; D010064:Embryo Implantation / Q000187:drug effects; D047108:Embryonic Development; D016193:G1 Phase / Q000187:drug effects; D042822:Genomic Instability; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D016160:Retinoblastoma Protein / Q000378:metabolism; D029607:Seminal Vesicle Secretory Proteins / Q000378:metabolism* / Q000494:pharmacology; D044967:Serum / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D016895:Culture Media, Serum-Free; D016213:Cyclins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D016160:Retinoblastoma Protein; D029607:Seminal Vesicle Secretory Proteins; C101178:Svs4 protein, rat; D005954:Glucosephosphate Dehydrogenase; D002374:Catalase; D011505:Protein-Tyrosine Kinases; D018844:Cyclin-Dependent Kinases