The effects of thyroparathyroidectomy and 1,25 dihydroxyvitamin D₃ on changes in the activities of some cytoplasmic and nuclear protein kinases during liver regeneration

Abstract

Partial hepatectomy (HPX), which proliferatively activates the remaining liver cells, triggered two transient prereplicative surges in the total activities of cytoplasmic types I and II cyclic AMP-dependent protein kinase holoenzymes, and of nuclear catalytic subunits from cyclic AMP-dependent protein kinases. It also induced a transient prereplicative increase in the activities of a nuclear Ca2+-calmodulin-stimulable, protamine-phosphorylating protein kinase, and a nuclear poly(L-lysine)-phosphorylating, 105 kDa protein kinase. Thyroparathyroidectomy (TPTX) delayed and reduced the first surge and completely eliminated the second surge of both of the cytoplasmic cyclic AMP-dependent protein kinases, reduced the rises in the activity of nuclear catalytic subunits, and completely eliminated the surge of the Ca2+-calmodulin-stimulable protein kinase, but did not affect the surge of the nuclear 105 kDa protein kinase. The impairment of the responses of the two cyclic AMP-dependent protein kinases to HPX in TPTX rats was not accompanied by a rise in the level of heat-stable inhibitor of cyclic AMP-dependent protein kinase activity. One intraperitoneal injection of 1,25-dihydroxyvitamin D1 into TPTX rats immediately after HPX completely restored the post-HPX surges in the activity of type I cyclic AMP-dependent protein kinase, but the hormone, even in high doses, had little or not effect on the type II isoenzyme or the nuclear Ca2+-calmodulin-stimulable, protamine-phosphorylating enzyme.

Vitamin D receptor ontogenesis in rat liver

“…The hormone 1,25(OH) 2 D 3 , either directly or through its calcaemic effects, also has effects on liver in the absence of the growth promotion that follows hepatectomy. Vitamin D deficiency significantly alters hepatic function (Sikorska et al 1983;Haddad et al 1987;Pahuja et al 1989). The hormone also stimulates the activity of isocitrate lyase and malate synthase, key enzymes in the glyoxylate cycle in the liver (Sikorska et al 1983;Davis et al 1990), increases the activity of the NADPH-dependent cytosolic triiodothyronine-binding protein in rat liver and in dRLh rat hepatoma-derived cells (Hashizume et al 1991) and enhances transferrin synthesis in primary cultures of rat hepatocytes (Taniguchi et al 1990).…”

Partial characterization of the mitogenic action of pp60v‐src, the oncogenic protein product of the src gene of avian sarcoma virus

“…Labeled cultures were washed twice with PBS containing 1 mM methionine, and the cells were scraped into the same buffer and transferred to cold tubes with washings, and finally centrifuged at 150 g for 5 minutes. Radioactivity precipitable by 20% trichloracetic acid was measured in each cell sample as described by Sikorska et al, (1983 Fig, 3. A short burst of pp(j0wS" activity was enough to stimulate were used to determine DNA-synthetic quiescent, serum-deprived tsLA23-NRK cells to transit GI and initiate DNA replication.…”

The normal liver harbors the vitamin D nuclear receptor in nonparenchymal and biliary epithelial cells

“…Baran et al 4,5 have shown that 1,25(OH) 2 D 3 increases intracellular Ca 2ϩ in rat hepatocytes, although the mode of action of the hormone in these studies may be due to a membrane receptor rather than the VDR n . 6 Studies performed in our laboratory 7,8 as well as by Whitfield et al 9,10 indicate that the liver responds to 1,25(OH) 2 D 3 , as indicated by its control of DNA polymerase ␣ activity as well as cytoplasmic and nuclear protein kinases leading to an accelerated regeneration process following two-thirds partial hepatectomy in the rat. The latter observations suggest that 1,25(OH) 2 D 3 has a significant effect on liver cell physiology during the compensatory growth process.…”