Biomaterial Database

Tumor necrosis factor-alpha stimulates lactate dehydrogenase A expression in porcine cultured sertoli cells: mechanisms of action. 1999

F Boussouar, and R Grataroli, and J Ji, and M Benahmed

INSERM, U-407, Faculté de Médecine Lyon-Sud, Oullins, France.

In the present study, we investigated the regulatory action of tumor necrosis factor-alpha (TNFalpha) on lactate dehydrogenase A (LDH A), a key enzyme involved in lactate production. To this end, use was made of a primary culture system of porcine testicular Sertoli cells. TNFalpha stimulated LDH A messenger RNA (mRNA) expression in a dose (ED50 = 2.5 ng/ml; 0.1 nM TNFalpha)-dependent manner. This stimulatory effect was time dependent, with an effect detected after 6 h of TNFalpha treatment and maximal after 48 h of exposition (5-fold; P<0.001). The direct effect of TNFalpha on LDH A mRNA could not be accounted for by an increase in mRNA stability (half-life = 9 h), but was probably due to an increase in LDH A gene transcription. Inhibitors of protein synthesis (cycloheximide), gene transcription (actinomycin D and dichlorobenzimidazole riboside), tyrosine kinase (genistein), and protein kinase C (bisindolylmaleimide) abrogated completely (actinomycin D, dichlorobenzimidazole riboside, cycloheximide, and genistein) or partially (bisindolylmaleimide) TNFalpha-induced LDH A mRNA expression. These observations suggest that the stimulatory effect of TNFalpha on LDH A mRNA expression requires protein synthesis and may involve a protein tyrosine kinase and protein kinase C. In addition, we report that LDH A mRNA levels were increased in Sertoli cells treated with FSH. However, although the cytokine enhances LDH A mRNA levels through increased gene transcription, the hormone exerts its stimulatory action through an increase in LDH A mRNA stability. The regulatory actions of the cytokine and the hormone on LDH A mRNA levels and therefore on lactate production may operate in the context of the metabolic cooperation between Sertoli and postmeiotic germ cells in the seminiferous tubules.

UI	MeSH Term	Description	Entries
D007527	Isoenzymes	Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.	Alloenzyme,Allozyme,Isoenzyme,Isozyme,Isozymes,Alloenzymes,Allozymes
D007770	L-Lactate Dehydrogenase	A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of LACTATE and PYRUVATE. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist.	Lactate Dehydrogenase,Dehydrogenase, L-Lactate,Dehydrogenase, Lactate,L Lactate Dehydrogenase
D008297	Male		Males
D011493	Protein Kinase C	An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.	Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D011500	Protein Synthesis Inhibitors	Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins.	Protein Synthesis Antagonist,Protein Synthesis Antagonists,Protein Synthesis Inhibitor,Antagonist, Protein Synthesis,Antagonists, Protein Synthesis,Inhibitor, Protein Synthesis,Inhibitors, Protein Synthesis,Synthesis Antagonist, Protein,Synthesis Inhibitor, Protein
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D003513	Cycloheximide	Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.	Actidione,Cicloheximide
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
D005640	Follicle Stimulating Hormone	A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Follicle-stimulating hormone stimulates GAMETOGENESIS and the supporting cells such as the ovarian GRANULOSA CELLS, the testicular SERTOLI CELLS, and LEYDIG CELLS. FSH consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity.	FSH (Follicle Stimulating Hormone),Follicle-Stimulating Hormone,Follitropin
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