Biomaterial Database

Role of tumor necrosis factor-alpha and the modulating effect of the caspases in rat corpus luteum apoptosis. 2003

Michael Abdo, and Susan Hisheh, and Arun Dharmarajan

School of Anatomy and Human Biology, The University of Western Australia, Crawley, Western Australia 6009, Australia.

Tumor necrosis factor-alpha (TNFalpha) is a pleiotropic cytokine that has been implicated in apoptosis of many cell systems. However, the signal transduction of TNFalpha during the structural and functional regression of the corpus luteum (CL) is largely unknown. In this study, we investigate the role of TNFalpha in rat CL apoptosis and the involvement of monocyte chemoattractant protein-1 (MCP-1) and the modulating effect of the caspases in this process. An in vivo study of CL during pregnancy and postpartum using immunohistochemistry and Western blot analysis indicated that increases in TNFalpha correspond with luteal apoptosis approaching term (Day 22) and at postpartum (Day 3). CL apoptosis was further investigated using a whole-CL culture model of tropic withdrawal. An increase was observed in both low molecular weight (MW) DNA fragmentation and TUNEL staining from 0 h to 8 h in culture. CL apoptosis in vitro was associated with increased protein expression of both TNFalpha and MCP-1 as measured by immunohistochemistry and Western blot analysis. Using a whole-CL culture model, apoptosis was induced in vitro by TNFalpha as demonstrated by a dose-dependent increase in DNA fragmentation. Treatment of luteal cells with TNFalpha and both specific caspase inhibitors (Z-DEVD-FMK, Z-VEID-FMK, Z-IETD-FMK) or a general caspase inhibitor (Boc-D-FMK) prevented the effect of TNFalpha. CL regression involves the apoptotic deletion of luteal cells; the results of this study suggest that TNFalpha is possibly involved in this process. The observed increases in MCP-1 expression suggest the coordination of TNFalpha expression with the infiltration and activation of macrophages. Furthermore, the results demonstrate the importance of the caspases in the TNFalpha signal transduction pathway and suggest a hierarchy within the caspase family.

UI	MeSH Term	Description	Entries
D011247	Pregnancy	The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.	Gestation,Pregnancies
D003338	Corpus Luteum	The yellow body derived from the ruptured OVARIAN FOLLICLE after OVULATION. The process of corpus luteum formation, LUTEINIZATION, is regulated by LUTEINIZING HORMONE.	Corpora Lutea,Lutea, Corpora
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005260	Female		Females
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014409	Tumor Necrosis Factor-alpha	Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.	Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha
D015153	Blotting, Western	Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.	Immunoblotting, Western,Western Blotting,Western Immunoblotting,Blot, Western,Immunoblot, Western,Western Blot,Western Immunoblot,Blots, Western,Blottings, Western,Immunoblots, Western,Immunoblottings, Western,Western Blots,Western Blottings,Western Immunoblots,Western Immunoblottings
D017209	Apoptosis	A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.	Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D046508	Culture Techniques	Methods of maintaining or growing biological materials in controlled laboratory conditions. These include the cultures of CELLS; TISSUES; organs; or embryo in vitro. Both animal and plant tissues may be cultured by a variety of methods. Cultures may derive from normal or abnormal tissues, and consist of a single cell type or mixed cell types.	Culture Technique,Technique, Culture,Techniques, Culture