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

• Published in: Journal of cellular physiology 2007-09, Vol.212 (3), p.610-625
• Main Authors: Morelli, Francesco, Peluso, Gianfranco, Petillo, Orsolina, Giannattasio, Angela, Filosa, Silvana, Motta, Chiara M., Tammaro, Stefania, Zatterale, Adriana, Calzone, Rita, Budillon, Alfredo, Cartenì, Maria, de Maria, Salvatore, Costanza, Maria R., Nigro, Antonella, Petrazzuolo, Marcella, Buommino, Elisabetta, Rizzo, Maria, Capasso, Giovanni, Baiano, Salvatore, Moscatiello, Francesco, Ravagnan, Gianpietro, Fuggetta, Maria P., Tajana, Gianfranco, Stiuso, Paola, Metafora, Bianca M., Metafora, Vittoria, Metafora, Salvatore
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - metabolism; Antioxidants - pharmacology; Apoptosis - drug effects; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Catalase - genetics; Catalase - metabolism; Cell Line, Tumor; Cell Proliferation - drug effects; Culture Media, Serum-Free - metabolism; Cyclin-Dependent Kinases - metabolism; Cyclins - metabolism; Cytotoxicity, Immunologic; DNA Fragmentation; Embryo Culture Techniques; Embryo Implantation - drug effects; Embryonic Development; G1 Phase - drug effects; Genomic Instability; Glucosephosphate Dehydrogenase - genetics; Glucosephosphate Dehydrogenase - metabolism; Humans; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - enzymology; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Mice; Mice, Inbred BALB C; Oxidative Stress; Phosphorylation; Protein-Tyrosine Kinases - metabolism; Rats; Rats, Wistar; Reactive Oxygen Species - metabolism; Resting Phase, Cell Cycle - drug effects; Retinoblastoma Protein - metabolism; RNA, Messenger - metabolism; Seminal Vesicle Secretory Proteins - metabolism; Seminal Vesicle Secretory Proteins - pharmacology; Serum - metabolism; Signal Transduction; Time Factors
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.21058

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. J. Cell. Physiol. 212:610–625, 2007. © 2007 Wiley‐Liss, Inc.