Related Experiment Videos
Juvenile hormones inhibit murine cell cycle progression and expression of type C viruses
Abstract:
Juvenile hormones (JH), congeners of retinoic acid, were examined for their capacity to inhibit cell cycle progression and chemically induced expression of endogenous xenotropic retrovirus in Kirsten sarcoma virus-transformed BALB (K-BALB) mouse cells. JHI, II, and III were found to inhibit induction of virus by 5-iododeoxyuridine (IUdR) and histidinol (Hdl) in a concentration-dependent fashion. Some inhibition of macromolecular synthesis was observed upon culture of the cells with JH; the most affected was RNA synthesis, which was reduced 27 to 40% within 4 h by the juvenoids. Epoxide hydrase (EH) activity, as determined by high-pressure liquid chromatography (HPLC), was present in amounts sufficient for the cells to convert the hormones metabolically to an ultimate form. A contact-inhibited K-BALB variant was synchronized by mitotic arrest and the cell cycle-specific effect of JHIII on virus induction during S phase was studied. JHIII added during G1 phase, and followed by induction, inhibited virus expression 95 and 76% by IUdR and Hdl, respectively. Induction was inhibited only 35% when JHIII was added during S phase concomitantly with the inducers and no inhibition was observed when JHIII was added during G2 phase followed by the inducers. JHIII added to synchronous cells in G1 phase inhibited progression of cells into S phase and the onset of DNA synthesis. The results indicate that mouse fibroblasts have a juvenile hormone-sensitive restriction point in G1 phase that might relate to the effects these hormones have on cell replication and differentiation.
Insights
Juvenile hormones (JH) inhibit viral expression and cell cycle progression in mouse cells. JHIII specifically blocks cells in G1 phase, impacting DNA synthesis and viral replication.
Area of Science:
- Cell Biology
- Virology
- Endocrinology
Background:
- Juvenile hormones (JH) are structurally related to retinoic acid.
- Kirsten sarcoma virus-transformed BALB (K-BALB) mouse cells are used to study viral expression.
- Understanding JH's role in cell cycle regulation and viral induction is crucial.
Purpose of the Study:
- To investigate the inhibitory effects of juvenile hormones (JH) on cell cycle progression.
- To examine JH's capacity to inhibit chemically induced expression of xenotropic retrovirus in K-BALB cells.
- To determine the cell cycle-specific effects of JHIII on viral induction.
Main Methods:
- K-BALB cells were treated with different concentrations of JHI, II, and III.
- Macromolecular synthesis (RNA, DNA) and epoxide hydrase (EH) activity were measured.
- Synchronized K-BALB cells were exposed to JHIII at specific cell cycle phases (G1, S, G2) before viral induction.
- Viral induction was assessed using 5-iododeoxyuridine (IUdR) and histidinol (Hdl).
Main Results:
- JHI, II, and III inhibited viral induction in a dose-dependent manner.
- JH treatment reduced RNA synthesis by 27-40% within 4 hours.
- JHIII added during G1 phase significantly inhibited viral expression (95% with IUdR, 76% with Hdl).
- JHIII added during G1 phase also inhibited cell progression into S phase and DNA synthesis.
Conclusions:
- Mouse fibroblasts possess a juvenile hormone-sensitive restriction point in the G1 phase.
- JH may influence cell replication and differentiation through this G1 restriction point.
- JH's inhibitory effects on viral replication are cell cycle-dependent, particularly in the G1 phase.