Abstract：
:The role of phospholipids (PLs) in the signal transduction pathways that are activated by a mitogenic stimulus (foetal calf serum) in Trypanosoma cruzi epimastigotes (EPI) was investigated. Only phosphatidylinositol-bis-phosphate was significantly altered in this process. Other phosphoinositides, including major PLs such as phosphatidylcholine and phosphatidylethanolamine, were unaltered. Lysophosphatidic acid, reported to be the primary active substance in effects of serum in other systems, had no mitogenic activity when added to epimastigote cultures. Involvement of phosphoinositide-specific phospholipase C was established using the inhibitors ET-18-OCH3 and U73122, which prevented phosphatidylinositol-bis-phosphate hydrolysis; the latter compound decreased T. cruz proliferation. The intracellular signalling downstream to the phospholipase C was mediated by Ca2+/PL-dependent protein kinase and Ca2+/calmodulin-dependent protein kinase II, judging from the marked decrease in replication caused by the specific inhibitors staurosporine, derythro-sphingosine and KN-93. Previous reports have demonstrated a dual control of cell growth in EPI, whose proliferation is stimulated by the activation of a phospholipase C system and inhibited by activation of an adenylate cyclase system. Investigating this 'cross-talk' phenomenon, we observed that an increase in intracellular cAMP inhibited growth mediated by a cAMP-dependent protein kinase, but did not cause PL alterations, and also did not prevent the effect of serum on them.
journal_name
Acta Tropjournal_title
Acta tropicaauthors
Malaquias AT,Oliveira MMdoi
10.1016/s0001-706x(99)00016-9subject
Has Abstractpub_date
1999-07-30 00:00:00pages
93-108issue
2eissn
0001-706Xissn
1873-6254pii
S0001-706X(99)00016-9journal_volume
73pub_type
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