[Different regulation of mitochondrial apoptosis and Bcl-2 gene expression in quescent and proliferative human fibroblasts infected with cytomegalovirus].
The aim of the study was to compare the dynamics ofmitochondrial apoptosis (MA) in cells at different stages of proliferation and with different susceptibility to cytomegalovirus (CMV). It has been found that in quiescent human fibroblasts (HF) CMV regulates MA at the level of bcl-2 gene transcription, exerting both pro- and anti-apoptotic effects. Suppression of bcl-2 transcription is greater in HF-977 line, which is highly susceptible to CMV in comparison with HF-1068 line. The effect of proliferative activity on MA was studied using CMV-infected HF-110044 line at the G0- or S-phase. A direct correlation was established between accumulation of cytochrome c and caspase 3 (MA markers) and production of IE72, pp65 and gB (CMV proteins). In G0-fibrob-lasts, viral replication was highly productive and bcl-2 expression was 10-fold as high as in S-phase cells, in which viral protein production and cell death were much lower. The increased gene transcription and accumulation of Bcl-2 protein enhanced cell viability and provided synthesis of viral proteins. Impaired structure of actin microfilaments, a caspase 3 target, coincided with pronounced suppression of gamma-actin gene in S-phase HF-110044. Our findings provide an insight into CMV-induced mechanisms of MA which lead to rapid death of infected quiescent fibroblasts and to slow death of cells infected at the stage of DNA synthesis.
Fedorova
N E
NE
Sokolova
T M
TM
Medzhidova
M G
MG
Kushch
A A
AA
D000199:Actins / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics*; D002460:Cell Line; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections / Q000235:genetics* / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology / Q000821:virology; D005786:Gene Expression Regulation; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D000199:Actins; D019253:Proto-Oncogene Proteins c-bcl-2