Growth control of differentiated fetal rat hepatocytes in primary monolayer culture. IX. Specific inhibition of DNA synthesis initiation by very low density lipoprotein and possible significance to the problem of liver regeneration.

Leffert, Hyam L.; Weinstein, David

doi:10.1083/jcb.70.1.20

Cited by 43 publications

(13 citation statements)

References 73 publications

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“…Although there are a number of studies describing lipoprotein inhibition of DNA synthesis for various cell types including a 3T3 fibroblast line (Ito et al, 1982;Leffert and Weinstein, 1976;Takii et al, 1983), in our system LDL does not diminish DNA synthesis unless it is oxidized. The inhibition by o-LDL of 3H-thymidine incorporation into DNA appeared to be distinct from o-LDL-induced cytotoxicity in that more severely oxidized LDL both blunted 3H-thymidine incorporation and caused cell death (Figs.…”

Section: Discussionmentioning

confidence: 88%

Toxicity of oxidized low‐density lipoprotein to cultured fibroblasts is selective for S phase of the cell cycle

Kosugi

Morel

DiCorleto

et al. 1987

Journal Cellular Physiology

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Oxidized LDL (o-LDL) is toxic to a variety of cultured cells. Preliminary results suggested that susceptibility is enhanced by cell proliferation. As a step toward determining the mechanism of cytotoxicity, we chose to identify the cell cycle phase(s) during which exposure of cultured human fibroblasts to o-LDL leads to death. Cytochalasin B, which blocks cell migration and proliferation, and irradiation, which prevents mitosis but not migration, both blocked cytotoxicity. Colchicine, which arrests cells in mitosis but does not inhibit DNA synthesis, did not block cytotoxicity. Treatment of cells with hydroxyurea, which blocks cells prior to S phase, prevented cell death. Addition of o-LDL to cells immediately after S phase allowed mitosis without death. The above results coupled with results using cells synchronized by three different means indicate that cell death is selective for proliferating cells and occurs after exposure to o-LDL during S phase. Understanding the mechanism of o-LDL-induced death may have implications for tissue damage in vivo in the numerous instances of pathology in which oxidized lipoproteins or lipids are present.

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Section: Discussionmentioning

confidence: 88%

Toxicity of oxidized low‐density lipoprotein to cultured fibroblasts is selective for S phase of the cell cycle

Kosugi

Morel

DiCorleto

et al. 1987

Journal Cellular Physiology

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“…These included the direct regeneration indexes of DNA synthesis, labeled nuclei and subsequent mitosis (3)(4)(5). Surrogate manifestations of regeneration also were monitored: systemic insulin and glucagon; circulating sex steroid hormones and their nuclear and cytosolic liver receptors (6)(7)(8)(9)(10)(11)(12); and the expression of transforming growth factor-p (TGF-P) mRNA (13, 141, c-Ha-rus mRNA (15) and c-jun mRNA (16,17). These changes after transplantation of small-for-size livers were compared with those occurring after transplantation of size-matched livers.…”

mentioning

confidence: 99%

Small-for-size liver transplanted into larger recipient: A model of hepatic regeneration

FRANCAVILLA¹

1993

Hepatology

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Orthotopic liver transplantation was performed in 60 recipient rats weighing 200 to 250 gm. Sixty rats of the same strain were used as liver donors, 30 weighing 100 to 140 gm (small for size) and the other 30 weighing 200 to 250 gm (same size). Mter 1, 2, 3, 4, 7 and 14 days (n = 5 each) DNA synthesis, nuclear thymidine labeling and mitoses were increased in both the smallfor-size and same-size groups, but significantly more in the former. These changes were maximal after 48 to 72 hr, similar to but later than the well-known regeneration response after partial hepatectomy, which peaks at 24 hr in rats. Indirect indexes of regeneration of the transplanted livers also were measured: plasma or serum ornithine decarboxylase; insulin and glucagon serum levels; estradiol and testosterone serum levels (and their nuclear and cytosolic receptors); and transforming growth factor-~, c-Ha-ras and c-jun mRNA expressions. With the small-for-size transplantation, these followed the same delayed pattern as the direct regeneration parameters. The small livers gradually increased in size over the course of 1 to 2 wk and achieved a volume equal to that of the liver originally present in the recipient. In contrast, no significant liver weight gain occurred in the transplanted livers from same-size donors despite the evidence of regeneration by direct indexes, but not by most of the surrogate parameters, including ornithine decarboxylase. (HEPATOLOGY 1993;19:210-216.) It has previously been demonstrated, both in human beings (1) and in dogs (2), that a liver from a small donor transplanted into a larger recipient undergoes hypertrophic and hyperplastic changes that result in a progressive increase of liver volume, until the trans-

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“…This lipid is probably bound to a carrier with much higher mole cular weight, since it was not dialyzed from the heated MCG3AF (table IV). Some authors have found that VLDL have immunosuppressive properties [15] and others that VLDL inhibit DNA synthesis [14], After removing VLDL from MCG3AF, however, its activ ity still remained (table V). This suggests that this activity cannot be attributed to these lipoproteins.…”

Section: Discussionmentioning

confidence: 99%

“…As Leffer and Weinstein [14] have reported, VLDL inhibit the initiation of DNA replication in embryonic hepatocytes. We removed these lipoproteins from the 70°C heated and dialyzed MCG3AF by partial delipidation, finding that this treatment did not ap preciably reduce the inhibitory activity of MCG3AF (table V).…”

Section: Additional Treatment Of Mcg3afmentioning

confidence: 99%

Detection of a Cell Proliferation-Inhibiting Factor in the Cell-Free Ascitic Fluid of Intraperitoneal Mouse Tumors

Olivares¹,

Rodriguez-Vedia²

1985

Oncology

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Three cell-free ascitic fluids: MCG3AF, P815AF and SL2AF were obtained from mice injected with MCG3, P815 and SL2 tumor cells, respectively. These ascitic fluids were tested in culture with different normal and tumor mouse cells showing an inhibitory effect on ³H-thymidine and ³H-uridine uptake. The MCG3AF, selected for further study, was tested with a larger number of mouse tumor cell lines and also with normal mouse and human cells. This ascitic fluid inhibited ³H-thymidine and ³H-uridine uptake in all cases. The cell proliferation-inhibiting factor(s) (CPIF) detected in MCG3AF was found to be thermostable and nondialyzable. Further biochemical analysis showed that CPIF is a lipid but with no relationship with very low-density lipoproteins.

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Growth control of differentiated fetal rat hepatocytes in primary monolayer culture. IX. Specific inhibition of DNA synthesis initiation by very low density lipoprotein and possible significance to the problem of liver regeneration.

Cited by 43 publications

References 73 publications

Toxicity of oxidized low‐density lipoprotein to cultured fibroblasts is selective for S phase of the cell cycle

Toxicity of oxidized low‐density lipoprotein to cultured fibroblasts is selective for S phase of the cell cycle

Small-for-size liver transplanted into larger recipient: A model of hepatic regeneration

Detection of a Cell Proliferation-Inhibiting Factor in the Cell-Free Ascitic Fluid of Intraperitoneal Mouse Tumors

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