Biomedical subjects

Z Kiss

Publications and source records attributed to Z Kiss.

At least 19 recordsLinked to original sources

PubMed2000

[Molecular biology follow-up of interferon therapy in patients with chronic myeloid leukemia].

In a prospective survey clinical haematological and molecular biological data of 31 patients with chronic myelogenous leukaemia (chronic phase, CML) observed in their haematological outpatient department were analyzed. During 1996 and 1999 a regular follow-up of the Philadelphia chromosome level in treated patients was performed with molecular biological techniques, i.e. with reverse transcription polymerase chain reaction (RT-PCR) and with fluorescence in situ hybridization (FISH) methods. During the follow-up period of 33 months from the 31 patients with CML (16 males, 15 females) 25 ones were treated with human recombinant interferon-alpha (IFN), however, six others were getting only hydroxyurea (HU). During this period in three patients allogen bone marrow transplantation was performed and seven ones expired (six out of them of blastic crisis). The quality of therapeutic response at cytogenetical level was determined by decrease of the bcr-abl level due to the treatment (non-responders, major, minor and complete cytogenetic remission groups). In nine patients (five from the IFN-group, four from the HU-group) achieved no cytogenetic therapeutic response (non-responders, 29%). However, in 13 patients a minor (bcr-abl range of 60-30%), and in nine patients a maior/complete (bcr-abl of 30-10%) cytogenetic response (42% and 29%, respectively) were detected. Moreover, the quality of cytogenetic response correlated with the haematological remission. The maior/complete cytogenetic response was durable in eigth patients. The improvement of the overall survival of patients with CML, the postpone of the fatal accelerated-blastic phase could be expected only from the early introduced, in individually adjusted and given in maximally tolerated dosage of interferon (3-5 million UI/m2/day). The qualitative (RT-PCR) and quantitative (FISH) detections of the Philadelphia chromosome are reliably reproducible up-to-date molecular biological methods getting relevant results, which could be very helpful in the planning, monitoring, in setting of optimal dosage of the interferon therapy of patients with CML, in addition in the judgement of the effectiveness of the therapy, in the reduction of adverse effects, as well as in forecasting of the cytogenetic progression.

Antineoplastic Agents↗

PubMed2000

Promitogenic effects of ethanol, methanol, and ethanolamine in insulin-treated fibroblasts.

The zinc-dependent potentiating effect of ethanol (EtOH) on insulin-stimulated DNA synthesis was studied with a focus on the possible site of EtOH action and the ability of other alcohols to elicit similar promitogenic effects. In serum-starved (27 hr) NIH 3T3 fibroblasts, 200-300 mM methanol (MeOH) and 0.1-1.5 mM ethanolamine (Etn), but not 3- to 9-carbon normal alcohols, enhanced the effect of insulin on DNA synthesis to varying extents. The promitogenic effects of EtOH and MeOH, but not that of Etn, required the presence of 15-25 microM zinc. The potentiating effects of Etn were enhanced by 5 mM choline (Cho) and inhibited by 1-3 mM hemicholinium-3 (HC-3), an inhibitor of Cho transporter and Cho kinase. In the presence of 15 microM zinc, 40 mM EtOH, which had no effect on its own, inhibited the potentiating effects of Cho and enhanced the inhibitory effects of HC-3 on synergistic stimulation of DNA synthesis by Etn and insulin. On the other hand, both Cho and HC-3 partially inhibited the promitogenic effect of 80 mM EtOH in the presence of 25 microM zinc. After a 10-min incubation, EtOH decreased the amount of cell-associated [(14)C]Cho in the absence but not in the presence of HC-3. After a 40-min incubation, Cho (5 mM) partially inhibited the cellular uptake as well as the metabolism of [(14)C]Etn. Whereas after the 40-min incubation 80 mM EtOH had no effects on Etn metabolism, in the absence of Cho it decreased the amount of cell-associated [(14)C]Etn. However, EtOH had no detectable effects on cell association of [(14)C]Etn after the 10-min incubation. The results suggest that in NIH 3T3 fibroblasts EtOH is a remarkably specific promitogen, and that it may act via a cell membrane site(s), also regulated by Cho (agonist) and HC-3 (antagonist), which can influence membrane binding and the promitogenic activity of Etn.

3T3 Cells↗

PubMed2000

Ethanol enhances the stimulatory effects of lysophosphatidic acid on DNA synthesis but not cell proliferation in human and mouse fibroblasts.

Lysophosphatidic acid (LPA), a constituent of serum, is a positive regulator of cell growth, while ethanol (EtOH) has been shown to exert both inhibitory and stimulatory effects on mitogenesis. In this work, we examined possible interactions between the effects of EtOH and LPA on DNA synthesis, cell proliferation, activating phosphorylation of p44/p42 mitogen-activated protein kinases (MAPK), and p70 S6 kinase (p70 S6K) activity. In fibroblasts derived from human or mouse embryo or the skin of healthy human subjects, LPA (1-20 microM) and EtOH (40-80 mM) synergistically stimulated DNA synthesis in a zinc-dependent manner. Nevertheless, EtOH did not modify the stimulatory effect of LPA on the proliferation of human embryonal fibroblasts. In the presence of zinc, EtOH did not affect LPA-induced activating phosphorylation of p42/p44 MAPKs, although an inhibitor of MAPK kinase inhibited the combined effects of LPA and EtOH on DNA synthesis. In contrast, in the presence of zinc, EtOH enhanced the stimulatory effect of LPA on p70 S6K activity. The results indicate that in human fibroblasts, in the presence of zinc, EtOH enhances the stimulatory effects of LPA on DNA synthesis, but not on cell proliferation, by a mechanism probably involving activation of p70 S6K.

3T3 Cells↗

PubMed2000

Ethanol has multiple effects on DNA synthesis in fibroblasts depending on the presence of secreted growth regulators and zinc as well as the level of protein kinase C activation.

Earlier we showed that in serum-starved (27 h), washed mouse fibroblasts and other cell lines 40-80 mM concentrations of ethanol (EtOH) potentiate, in a zinc (Zn2+)-dependent manner, the combined stimulatory effects of calcium (Ca2+) and insulin (Ins) on DNA synthesis. We now report that the promitogenic EtOH effects require removal of the used medium at least 6 h prior to treatments with EtOH, Zn2+, and Ins. If serum-starved (27 h) cells were continuously incubated for another 18-h period without replacing the medium, a secreted cellular factor moderately enhanced the mitogenic effect of Ins and simultaneously blocked the potentiating effect of EtOH on DNA synthesis measured during the last hour of treatments. However, the presence of Ca2+ (2.8 mM) plus Zn2+ (25 microM) or 25-300 nM phorbol 12-myristate 13-acetate (PMA) during the serum starvation period partially restored the promitogenic effect of EtOH. The PMA effect was blocked by the protein kinase C (PKC) inhibitor GF 109203X added for the second (18 h) period. Even at 300 nM, PMA failed to fully downregulate PKC-alpha, the major PKC isoform, over a 28-h period, suggesting that an activated PKC enzyme was involved in the restoration of EtOH effect. When EtOH (40-80 mM) was added for the entire serum starvation period and the incubations were continued for 18 h without removing the medium, EtOH inhibited both the combined actions of Ins and cellular factor as well as the promoting effect of newly added EtOH on Ins-dependent DNA synthesis. Coaddition of Zn2+ and PMA with EtOH prevented these inhibitory effects of EtOH. The results indicate that in mouse fibroblasts EtOH can both enhance and inhibit Ins-dependent DNA synthesis depending on the timing of EtOH treatment as well as the presence of Zn2+, cellular factors, and activators of the PKC system.

3T3 Cells↗

PubMed2000

[Experiences with josamycin therapy in dermatologic diseases].

Josamycin belongs to the new generation of macrolide antibiotics. Josamycin treatment was applied to various dermatological diseases (acne, pyoderma) and sexually transmitted bacteriological infections. During the examinations in ambulance treatment, 26 patients out of a total of 55 became completely healthy, 27 got better and in case of 2 persons, their conditions did not change. 4 of the sick people reported of side effects. According to the author, josamycin could be a favourable choice in certain dermatological pathographies and sexually transmitted infections because of its effectiveness and good tolerance.

Acne Vulgaris↗

PubMed2000

alpha(1)-antitrypsin can increase insulin-induced mitogenesis in various fibroblast and epithelial cell lines.

alpha(1)-Antitrypsin (AT), the archetypal member of the superfamily of serine proteinase inhibitors, inhibits leukocyte elastase activity and thereby can prevent lung damage. Here we show that in fibroblasts from human fetal lung and mouse embryo as well as in certain epithelial cells AT can also enhance the stimulatory effects of insulin on DNA synthesis and cell proliferation. Warming of AT at a moderate (41 degrees C) temperature for a longer time (21 h) or at a higher (65 degrees C) temperature for 30 min before treatment increased its stimulatory effects on both DNA synthesis and activating phosphorylation of p42/p44 mitogen-activated protein kinases. The results suggest that AT may promote regeneration of damaged tissues under pathophysiological conditions which are associated with fever.

Alkaline Phosphatase↗

PubMed2000

Protein kinase C-stimulated formation of ethanolamine from phosphatidylethanolamine involves a protein phosphorylation mechanism: negative regulation by p21 Ras protein.

Mammalian cells express a phospholipase D (PLD)-like enzyme which forms ethanolamine from phosphatidylethanolamine (PtdEtn) by a protein kinase C-alpha (PKC-alpha)-activated, presently unknown, mechanism. Now we report that addition of a PKC-alpha-enriched purified PKC preparation or recombinant PKC-alpha to a plasma membrane-enriched membrane fraction, isolated from leukemic HL60 cells, greatly ( approximately 6.5-fold stimulation) enhanced PtdEtn hydrolysis if the PKC activator phorbol 12-myristate 13-acetate (PMA) and ATP were both present; this was accompanied by PKC-mediated phosphorylation of several membrane proteins. The combined effects of PKC-alpha, ATP, and PMA on [(14)C]PtdEtn hydrolysis were inhibited by GF 109203X (10 microM), an inhibitor of catalytic activity of PKC. In this membrane fraction, PMA alone also had a smaller ( approximately 3.5-fold) stimulatory effect on PtdEtn hydrolysis which was not affected by adding ATP or GF 109203X to the membranes. These results suggest that PMA can stimulate PtdEtn hydrolysis via a PKC-catalyzed phosphorylation mechanism as well as by a phosphorylation-independent process. Transformation of NIH 3T3 fibroblasts by H-ras reduced the effect of PMA on PtdEtn hydrolysis. Furthermore, in NIH 3T3 fibroblasts, scrape-loaded Y13-259 anti Ras antibody enhanced PMA-stimulated hydrolysis of PtdEtn. These results suggest that activation of the PtdEtn-hydrolyzing PLD enzyme by PKC-alpha is inhibited by p21 Ras.

3T3 Cells↗

PubMed2000

Growth factor-like effects of placental alkaline phosphatase in human fetus and mouse embryo fibroblasts.

Human placental alkaline phosphatase (PALP) is synthesized in the placenta during pregnancy and is also expressed in many cancer patients; however, its physiological role is unknown. Here we show that in human fetus fibroblasts as well as normal and H-ras-transformed mouse embryo fibroblasts PALP stimulates DNA synthesis and cell proliferation in synergism with insulin, zinc and calcium. The mitogenic effects of PALP are associated with the activation of c-Raf-1, p42/p44 mitogen-activated protein kinases, p70 S6 kinase, Akt/PKB kinase and phosphatidylinositol 3'-kinase. The results suggest that in vivo PALP may promote fetus development as well as the growth of cancer cells which express oncogenic Ras.

3T3 Cells↗

PubMed2000

Ethanol, Zn2+ and insulin interact as progression factors to enhance DNA synthesis synergistically in the presence of Ca2+ and other cell cycle initiators in fibroblasts.

In serum-starved NIH 3T3 fibroblasts, ethanol (30-80 mM) promoted the effects of insulin and insulin-like growth factor I (IGF-I) on DNA synthesis in a Zn(2+)-dependent manner. Ethanol and Zn(2+) were most effective when added shortly before or after insulin, indicating that all these agents facilitated cell cycle progression. The synergistic effects of ethanol, Zn(2+) and insulin (or IGF-I) on DNA synthesis required 1.1-2.3 mM Ca(2+), which seemed to act as the cell cycle initiator. When serum-starved cells were pretreated for 2 h with other cell cycle initiators such as 10% (v/v) serum, 50 ng/ml platelet-derived growth factor or 2 ng/ml fibroblast growth factor, subsequent co-treatments with 60 mM ethanol, Zn(2+) and insulin for an 18 h period again synergistically increased DNA synthesis. Of the various signal transducing events examined, ethanol stimulated cellular uptake of (45)Ca and it enhanced the stimulatory effects of insulin on p70 S6 kinase activity in a Zn(2+)-dependent manner. In contrast, ethanol inhibited insulin-induced activating phosphorylation of p42/p44 mitogen-activated protein kinases; these inhibitory ethanol effects were prevented by Zn(2+). The results show that, in NIH 3T3 fibroblasts, ethanol can promote cell cycle progression in the presence of a cell cycle initiator as well as Zn(2+) and insulin (or IGF-I).

Animals↗

PubMed2000

Expression of human choline kinase in NIH 3T3 fibroblasts increases the mitogenic potential of insulin and insulin-like growth factor I.

In mammalian cells, growth factors, oncogenes, and carcinogens stimulate phosphocholine (PCho) synthesis by choline kinase (CK), suggesting that PCho may regulate cell growth. To validate the role of PCho in mitogenesis, we determined the effects of insulin, insulin-like growth factor I (IGF-I), and other growth factors on DNA synthesis in NIH 3T3 fibroblast sublines highly expressing human choline kinase (CK) without increasing phosphatidylcholine synthesis. In serum-starved CK expressor cells, insulin and IGF-I stimulated DNA synthesis, p70 S6 kinase (p70 S6K) activity, phosphatidylinositol 3-kinase (PI3K) activity, and activating phosphorylation of p42/p44 mitogen-activated protein kinases (MAPK) to greater extents than in the corresponding vector control cells. Furthermore, the CK inhibitor hemicholinium-3 (HC-3) inhibited insulin- and IGF-I-induced DNA synthesis in the CK overexpressors, but not in the vector control cells. The results indicate that high cellular levels of PCho potentiate insulin- and IGF-I-induced DNA synthesis by MAPK- and p70 S6K-regulated mechanisms.

3T3 Cells↗

PubMed2000

Placental alkaline phosphatase, insulin, and adenine nucleotides or adenosine synergistically promote long-term survival of serum-starved mouse embryo and human fetus fibroblasts.

Earlier we showed that in serum-starved fibroblasts placental alkaline phosphatase (PALP) can exert growth factor-like effects. Here we report that in mouse embryo (NIH 3T3) and human fetus (HTB-157) fibroblasts, PALP (200 nM) alone provided full protection against serum starvation-induced cell death for 5 days. After 12 days, substantial effects of PALP on cell survival required the copresence of insulin (500 nM) and ATP or adenosine (100 microM). In serum-starved NIH 3T3 cells, PALP induced activating phosphorylation of p42/p44 mitogen-activated protein (MAP) kinases; insulin, but not ATP, had small additional effects. PALP also stimulated the expression of various cyclins; ATP both prolonged and enhanced PALP-induced expression of cyclins A and E. Finally, ATP/adenosine enhanced activation of Akt kinase by insulin. The results suggest that PALP may be a regulator of growth and remodeling of fetal tissues during the second and third trimester of pregnancy when it is expressed.

3T3 Cells↗

PubMed1999

The possible mechanism of synergistic effects of ethanol, zinc and insulin on DNA synthesis in NIH 3T3 fibroblasts.

In serum-starved NIH 3T3 fibroblast cultures, zinc (15-40 microM) enhanced both the individual and combined stimulatory effects of insulin and ethanol (EtOH) on DNA synthesis. Zinc, but not EtOH, also promoted the stimulatory effects of insulin on activating phosphorylation of p42/p44 mitogen-activated protein (MAP) kinases. In the presence of zinc, insulin induced premature expression of cyclin E during early G1 phase; EtOH partially restored the normal timing (late G1 phase) of cyclin E expression. The results suggest that zinc and EtOH promote insulin-induced DNA synthesis by different mechanisms; while zinc acts by enhancing the effects of insulin on MAP kinase activation, EtOH may act by ensuring timely zinc-dependent insulin-induced expression of cyclin E.

3T3 Cells↗

PubMed1999

Ethanol potentiates the mitogenic effects of sphingosine 1-phosphate by a zinc- and calcium-dependent mechanism in fibroblasts.

In mouse embryo NIH 3T3 fibroblasts, ethanol (60-80 mM) was found to enhance the stimulatory effects of sphingosine 1-phosphate (S1P) on both DNA synthesis and cell proliferation. Well-detectable potentiating effects of ethanol on S1P-induced mitogenesis required the presence of calcium (>1 mM) and zinc (20-40 microM) in the incubation medium. The amphibian tetrapeptide bombesin, which is known to mobilize intracellular calcium in fibroblasts, had no effect alone, but it approximately doubled the combined stimulatory effects of ethanol and S1P on DNA synthesis. The synergistic mitogenic effects of ethanol and S1P were also slightly enhanced, rather than inhibited, by the alcohol dehydrogenase inhibitor 4-methylpyrazole (5 mM). Of the various growth regulatory enzymes examined, ethanol detectably enhanced the stimulatory effects of S1P on the phosphosphorylation (activation) of p42/p44 mitogen-activated protein (MAP) kinases, but not of p38 MAP kinase. Cotreatment of fibroblasts with ethanol for 10 min also enhanced the stimulatory effects of S1P on the activities of c-Raf-1 kinase and p70 S6 kinase, but neither S1P nor ethanol had effects on phosphatidylinositol 3'-kinase and Akt/PKB kinase activities. Ethanol-plus-S1P-induced DNA synthesis was partially inhibited by both PD 98059 (50 microM) and rapamycin (10 nM), inhibitors of p42/p44 MAP kinase kinase and mTOR/p70 S6 kinases, respectively. The results indicate that in NIH 3T3 fibroblasts, ethanol can enhance the mitogenic effects of S1P by a zinc- and calcium-dependent mechanism involving both the rapamycin-sensitive p70 S6 kinase-dependent and the c-Raf-1/MAP kinase-dependent growth regulatory pathways.

3T3 Cells↗

PubMed1999

Anandamide stimulates phospholipase D activity in PC12 cells but not in NIH 3T3 fibroblasts.

The endogenous cannabinoid arachidonoylethanolamide was previously reported to have no effects on the phospholipase D activity in Chinese hamster ovary cells expressing the human brain-specific cannabinoid receptor, while in mouse peritoneal cells, delta9-tetrahydrocannabinol stimulated this enzyme. In this work, arachidonoylethanolamide (0.1-1 microM) was found to stimulate the phospholipase D-mediated phospholipid hydrolysis in rat adrenal pheochromocytoma PC12 cells, but not in mouse NIH 3T3 fibroblasts. The phospholipase D-activating effects of arachidonoylethanolamide were comparable to those elicited by phorbol ester and nerve growth factor, while arachidonic acid (1 microM) had no effects. The results show that, depending on the cell type, arachidonoylethanolamide can be an activator of the phospholipase D system.

3T3 Cells↗

PubMed1999

Overexpression of protein kinase C-epsilon and its regulatory domains in fibroblasts inhibits phorbol ester-induced phospholipase D activity.

In fibroblasts, the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) stimulates phospholipase D (PLD)-mediated hydrolysis of both phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEtn) by PKC-alpha-mediated nonphosphorylating and phosphorylating mechanisms. Here we have used NIH 3T3 fibroblasts overexpressing holo PKC-epsilon and its regulatory, catalytic, and zinc finger domain fragments to determine if this isozyme also regulates PLD activity. Overexpression of holo PKC-epsilon inhibited the stimulatory effects of PMA (5-100 nM) on both PtdCho and PtdEtn hydrolysis. Overexpression of PKC-epsilon also was found to inhibit platelet-derived growth factor-induced PLD activity. Expression of the catalytic unit of PKC-epsilon had no effect on PMA-induced PLD activity. In contrast, expression of both the regulatory domain fragment and the zinc finger domain of PKC-epsilon resulted in significant inhibition of PMA-stimulated PtdCho and PtdEtn hydrolysis. Interestingly, although PKC-alpha also mediates the stimulatory effect of PMA on the synthesis of PtdCho by a phosphorylation mechanism, overexpression of holo PKC-epsilon or its regulatory domain fragments did not affect PMA-induced PtdCho synthesis. These results indicate that the PKC-epsilon system can act as a negative regulator of PLD activity and that this inhibition is mediated by its regulatory domain.

3T3 Cells↗

PubMed1999

Bombesin promotes synergistic stimulation of DNA synthesis by ethanol and insulin in fibroblasts.

In NIH 3T3 fibroblasts and several other cellular systems, ethanol (50-80 mM) was previously shown to greatly enhance the mitogenic effects of insulin particularly in the presence of zinc. Here we report that in NIH 3T3 fibroblasts the combined stimulatory effects of ethanol and insulin on DNA synthesis can be further increased by bombesin both in the absence and presence of zinc. Bombesin also enhanced insulin-plus-ethanol-induced DNA synthesis in mouse Swiss 3T3 and Balb/c 3T3 fibroblasts, but in these cells bombesin was effective only in the presence of zinc. In NIH 3T3 fibroblasts, the potentiating effects of ethanol on insulin-induced DNA synthesis by the zinc-dependent and bombesin-dependent mechanisms were additive. Wortmannin, an inhibitor of phosphatidylinositol 3'-kinase (PI3K), prevented the comitogenic effect of ethanol in the presence of bombesin but not in the presence of zinc. Furthermore, bombesin, but not ethanol, was found to enhance the stimulatory effect of insulin on PI3K activity. Rapamycin, an indirect inhibitor of p70 S6 kinase actions, inhibited the comitogenic effects of ethanol in the presence of both zinc and bombesin. However, only ethanol, but not bombesin, enhanced the stimulatory effect of insulin on p70 S6 kinase activity; this effect of ethanol was zinc-dependent. Neither ethanol nor bombesin enhanced the stimulatory effects of insulin on the phosphorylation (activation) of p38/p42/p44 mitogen-activated protein kinases. The results suggest that in mouse fibroblasts maximal stimulation of DNA synthesis by physiologically relevant concentrations of ethanol occurs if both PI3K and p70 S6 kinase are activated. These data suggest a mechanism by which ethanol may affect growth in affected human tissues during its tumor promoting actions.

3T3 Cells↗

PubMed1999

Regulation of mitogenesis by water-soluble phospholipid intermediates.

Many recent observations implicate choline and ethanolamine kinases as well as phosphatidylcholine-specific phospholipase C in the regulation of mitogenesis and carcinogenesis. For example, human cancers generally contain high concentrations of phosphoethanolamine and phosphocholine, and in different cell lines various growth factors, cytokines, oncogenes and chemical carcinogens were all shown to stimulate the formation of phosphocholine and phosphoethanolamine. In addition, other reports have appeared showing that both extracellular and intracellular phosphocholine as well as ethanolamine and its derivatives can regulate cell growth. This area of research has clearly arrived at a stage when it becomes important to examine critically the feasibility of water-soluble phospholipid intermediates serving as potential regulators of cell growth in vivo. Accordingly, the goal of this review is to summarise available information relating to the formation and mitogenic actions of intracellular and extracellular phosphocholine as well as ethanolamine and its derivatives.

3T3 Cells↗

PubMed1999

Extracellular calcium stimulates DNA synthesis in synergism with zinc, insulin and insulin-like growth factor I in fibroblasts.

In serum-starved mouse NIH 3T3 fibroblasts cultured in 1.8 mM Ca2+-containing medium, addition of 0.75-2 mM extra Ca2+ stimulated DNA synthesis in synergism with zinc (15-60 microM), insulin and insulin-like growth factor I. Extra Ca2+ stimulated phosphorylation/activation of p42/p44 mitogen-activated protein kinases by an initially (10 min) zinc-independent mechanism; however, insulin, and particularly zinc, significantly prolonged Ca2+-induced mitogen-activated protein kinase phosphorylation. In addition, extra Ca2+ activated p70 S6 kinase by a zinc-dependent mechanism and enhanced the stimulatory effect of zinc on choline kinase activity. Insulin and insulin-like growth factor I also commonly increased both p70 S6 kinase and choline kinase activities. In support of the role of the choline kinase product phosphocholine in the mediation of mitogenic Ca2+ effects, cotreatments with the choline kinase substrate choline (250 microM) and the choline kinase inhibitor hemicholinium-3 (2 mM) enhanced and inhibited, respectively, the combined stimulatory effect of extra Ca2+ (3.8 mM total) and zinc on DNA synthesis. In various human skin fibroblast lines, 1-2 mM extra Ca2+ also stimulated DNA synthesis in synergism with zinc and insulin. The results show that in various fibroblast cultures, high concentrations of extracellular Ca2+ can collaborate with zinc and certain growth factors to stimulate DNA synthesis. Considering the high concentration of extracellular Ca2+ in the dermal layer, Ca2+ may promote fibroblast growth during wound healing in concert with zinc, insulin growth factor-I insulin, and perhaps other growth factors.

3T3 Cells↗