The regulation of hydroxymethylglutaryl-CoA reductase in cultured cells

Cyclic fluctuations of 3‐hydroxy‐3‐methylglutaryl‐CoA reductase in aortic smooth muscle cell cultures

“…These results partially agree with the previous observation in synchronized cell cultures, with two peaks occurring 24 h prior to or at the time of the S phase (24), and also agree with the cyclic variations of reductase activity in dThd block synchronized cells with maximal activity in S or G 2 /M phases (26). However, these findings contrast with those of Tavangar et al (14), who stated that this variation in reductase activity is associated only with feeding the cells.…”

“…On the other hand, several investigators have observed that HMG-CoA reductase activity is high in rapidly dividing cells but declines as cells reach confluence (28,29). This view contrasts with the results reported previously (14) since these authors reported that reductase activity increased in confluent cells where no transient changes in DNA synthesis or in cell number were observed. Also, marked fluctuations during the various phases of the cell cycle have been reported in HMG-CoA reductase activity, in the G 1 phase when quiescent, growth-inhibited cells are stimulated by replenishment of growth factors or serum in synchronized cultures (29), increasing to twice that of the unsynchronized cells examined concomitantly.…”

“…However, parallel changes in HMG-CoA reductase activity have been observed in synchronized and unsynchronized cells (14). In fact, HMG-CoA reductase activity was low at the time of the medium change and increased 10-to 20-fold 5-10 h after medium change, returning to basal levels by 24 h in both synchronized and unsynchronized cells.…”

“…However, chick liver and intestine reductase do not show diurnal rhythm at hatching (5) or during the first week of life, when the chick is still reabsorbing the yolk (12) and thereby developing a transient hypercholesterolemia, which becomes almost three times higher in cholesterol-fed chicks (13). Indeed, the rise in reductase activity is depressed in hypercholesterolemic chicks (13) and following cholesterol or mevalonate feeding in cell cultures (14). Moreover, the diurnal rhythm of mevalonate metabolism by sterol and nonsterol pathways and of mevalonate-activating enzymes has been demonstrated (15).…”

“…Early experiments (27) demonstrated a small increase of the reductase activity in cultured fibroblasts 19 h after changing to fresh media supplemented with FBS, whereas a large (fivefold) increase occurred in reductase activity after changing to fresh media supplemented with lipoprotein-deficient serum (LPDS). Moreover, early experiments (14) also demonstrated that HMG-CoA reductase activity increased in a murine macrophage-like cell line (J774) under normal culture conditions (in the presence of 10% FBS) and that this variation was associated with feeding the cells. These authors also demonstrated the increase of reductase activity in confluent and unsynchronized cultures, emphasizing that other exogenous factors besides the cell cycle could play a role.…”