Cell cycle regulatory proteins in the liver in murine Trypanosoma cruzi infection.
The liver is an important target of Trypanosoma cruzi infection. Infection of CD-1 mice with T. cruzi (Brazil strain) resulted in parasitism of the liver, primarily in sinusoidal and Kupffer cells. Immunoblot analysis revealed activation of extra cellular signal-regulated kinase (ERK) during the acute and subacute period of infection, but p38 mitogen activated kinase (MAPK) and JNK were not activated. The activity of important cell cycle regulatory genes was also examined in the liver following infection. There was increased expression of cyclin D1, cyclin E and cyclin A as well as proliferating cell nuclear antigen (PCNA) at 45, 60 and 215 days post infection. In addition, the levels of the cyclin-dependent kinase inhibitors p27(KIP1), p21(WAF1) and the tumor suppressor p53 were increased in the livers obtained from infected mice. Quantitative PCR revealed increased abundance of mRNA for cyclins A, D1 and E. Interestingly, cyclin A and E are ordinarily not found in the adult liver. Thus infection caused a reversion to a fetal/neonatal phenotype. These data provide a molecular basis for cell proliferation in the liver following T. cruzi infection.
Bouzahzah
Boumediene
B
Department of Pathology at Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Nagajyothi
Fnu
F
Desruisseaux
Mahalia S
MS
Krishnamachary
Mohan
M
Factor
Stephen M
SM
Cohen
Alex W
AW
Lisanti
Michael P
MP
Petkova
Stefka B
SB
Pestell
Richard G
RG
Wittner
Murray
M
Mukherjee
Shankar
S
Weiss
Louis M
LM
Jelicks
Linda A
LA
Albanese
Chris
C
Tanowitz
Herbert B
HB
D000818:Animals; D018797:Cell Cycle Proteins / Q000032:analysis* / Q000235:genetics; D049109:Cell Proliferation; D014355:Chagas Disease; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000032:analysis; D016213:Cyclins / Q000032:analysis / Q000235:genetics; D008099:Liver / Q000737:chemistry / Q000469:parasitology* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D014349:Trypanosoma cruzi; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D018797:Cell Cycle Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016213:Cyclins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53