Phorbol ester-stimulated murine myelopoiesis: role of colony-stimulating factors

Tumor promoting phorbol esters, such as 12-0-tetradecanoyl-phorbol-13-acetate (TPA), stimulate colony formation in vitro by murine granulocyte-macrophage progenitors (GM-CFC) without added colony stimulating factors (CSF). To determine whether TPA induces CSF production in vitro, marrow cells were cultured for 1 to 7 days in liquid medium with or without TPA. No CSF was detected in any sample by a double antibody radioimmunoassay (sensitivity = 2 units/0.1 ml), however, colony-stimulating activity was detected in supernatant fluid from all TPA containing cultures by bioassay. This activity appeared to result from a direct effect of TPA rather than from production of CSF, as equivalent activity was found in TPA-containing medium incubated in the absence of marrow cells. Rabbit antiserum to purified L-cell CSF inhibited colony formation stimulated by L-cell CSF and WEHI-3 CSF, but had no effect on colony formation induced by TPA. Cells from long-term marrow cultures responded to TPA with colony formation, despite culture conditions and cell fractionation procedures that reduced the frequency of CSF-producing macrophages to less than 1.0%. TPA inhibited binding of radioiodinated L-cell CSF to marrow cells, especially if the cells were first exposed to TPA. These results do not support induction of CSF production as the major mechanism of phorbol ester stimulation of myelopoiesis. Phorbol esters may directly stimulate GM-CFC and/or enhance their response to CSF by a mechanism involving CSF binding sites.     

Mononuclear macrophage (M-CFC) colony formation in semisolid media in the absence of exogenous GM-CSF

Human fetal bone marrow (FBM) cells were examined for the ability to form colonies in the absence of exogenous colony-stimulating factor (CSF) in double layer agar, methylcellulose (MC), and in agar-MC (agar underlayer, MC overlayer) culture systems. Without exogenous CSF, macrophage colonies (M-CFC) were formed in a combined culture of agar and MC. Aggregates of 5-40 cells were observed on day 7. Gradually, large compact colonies which survived for 10-12 weeks of cultivation, were formed. They were composed of mononuclear monocytes and multinucleated cells. M-CFC progenitors were nonadherent, but their progeny became adherent during differentiation within the colony. Colony formation was cell-dose-dependent. Depletion of monocytes increased the number of colonies in agar-MC cultures and stimulated the development of some macrophage colonies in MC. Survival of monocyte progenitors was not dependent on CSF. Neither was their proliferation nor partial differentiation in agar-MC cultures. CSF increased M-CFC colony efficiency, however, if it was present when cultures were initiated. Addition of CSF to M-CFC growing for 2-5 weeks in CSF-deprived medium stimulated monocytes proliferation and transformation into macrophages. Epithelioid cells, an increase in the number of giant multinucleated cells, and granulocyte multiplication were also observed. The absolute dependence of macrophage colony formation on CSF described by others might be a result of inadequate culture conditions due to agar rather than an intrinsic physiological requirement.     

锂对小鼠高增殖潜能集落形成细胞和粒巨噬系祖细胞体外增殖的影响

本文观察了锂对ＢＡＬＢ／Ｃ小鼠骨髓高增殖潜能集落形成细胞（ＨＰＰ－ＣＦＣ）和粒巨噬系祖细胞ＣＦＵ－ＧＭ体外增殖的影响。ＨＰＰ－ＣＦＣ集落由ＩＬ－１、ＩＬ－６、ＷＥＨＩ３条件培养液（ＷＥＨＩ３－ＣＭ,含有ＩＬ－３）及Ｌ９２９条件培养液（Ｌ９２９－ＣＭ,含有Ｍ－ＣＳＦ）所支持,而ＣＦＵ－ＧＭ由ＷＥＨＩ３－ＣＭ所支持。结果显示,ＬｉＣｌ浓度在０．４－２ｍｍｏｌ／Ｌ时呈现剂量依赖性抑制ＨＰＰ－ＣＦＣ增殖;而在０．４－１ｍｍｏｌ／Ｌ的浓度范围内,则对ＣＦＵ－ＧＭ的增殖起剂量依赖性促进作用。这些结果提示ＬｉＣｌ对ＨＰＰ－ＣＦＣ和ＣＦＵ－ＧＭ的作用不同,可能锂有诱导ＨＰＰ－ＣＦＣ向成熟细胞分化的作用     

CSF-responsive bone marrow cells in liquid culture: characterization and screening applications

In a previous study, colony-stimulating factor (CSF) activity assayed in colony culture correlated closely with 3HTdR uptake by human marrow cells depleted of adherent cells. To use this assay for screening media for CSF and immunotoxins for marrow toxicity, cells growing in liquid culture were compared to conventional granulocyte/macrophage (CFU-gm) colony assays. CSF dose-response relationships for liquid and colony-forming assays were nearly identical. 3HTdR uptake by nonadherent marrow cells was CSF dose-related, and there was a linear relationship between number of cells cultured and 3HTdR uptake. Ricin cytotoxicity curves for liquid cultures and CFU-gm were identical on day 7 but showed some disparity with day 14 cultures. Results with all cultures showed 3HTdR uptake to be most closely correlated with CFU-gm colony, rather than cluster, growth. Myeloid cell differentiation in liquid culture was similar to colony cultures, producing mixtures of granulocytes, macrophages and eosinophils. By combining cell and differential counts, production of various myeloid cells could be quantitated. Cytotoxicity of anti-Ia for CFU-gm and liquid culture cells was compared and the majority of both cell populations expressed Ia-like antigens. Simultaneous staining for surface antigens and DNA content was used to characterize proliferating marrow cells, and the vast majority of cells expressed myeloid markers. Transferrin receptors were displayed by cells in S/G2/M and appeared after CSF stimulation on G0/G1 cells. We conclude liquid cultures can be used to screen conditioned media for human CSF and to screen for cytotoxicity to normal myeloid precursor cells. Behavior of CSF-responsive cells in liquid culture appears most closely related to that of CFU-gm colony-forming cells, and characterization of CSF-stimulated cells allows quantitative as well as qualitative estimates of myeloid cell production.     

锂和三尖杉酯碱对HL—60细胞增殖,分化和c—myc表达的影响

本研究利用细胞培养技术观察了氯化锂和三尖杉酯碱（ＨＴ）对ＨＬ－６０细胞增殖的影响,不同浓度的氯化锂对ＨＬ－６０细胞的集落形成和３Ｈ－ＴｄＲ参入均呈剂量依赖式抑制;三尖杉酯碱亦有类似的作用。在培养体系中加氯化锂和三尖杉酯碱时,对ＨＬ－６０细胞数及集落形成抑制作用与单用二者相比较有明显增加。用ＮＢＴ还原试验,氯化锂和三尖杉酯碱均促进ＨＬ－６０细胞的分化,小剂量氯化锂还能加强三尖杉酯碱对ＨＬ－６０细胞诱导分化作用。从氯化锂和三尖杉酯碱处理的ＨＬ－６０细胞中提取总ＲＮＡ,应用ＲＴ／ＰＣＲ检测ｃ－ｍｙｃ的表达,结果表明经氯化锂和三尖杉酯碱处理的ＨＬ－６０细胞ｃ－ｍｙｃ表达均降低,与未处理的ＨＬ－６０细胞ｃ－ｍｙｃ比较,说明氯化锂和三尖杉酯碱均能抑制ｃ－ｍｙｃ的表达,提示ｃ－ｍｙｃ很可能在白血病细胞增殖、分化中起调控作用。     

Effects of human leukocyte conditioned medium on mouse haemopoietic progenitor cells.

Medium conditioned by human peripheral blood leukocytes (HLCM) was studied for its in vitro effects on haemopoietic progenitor cells (CFU-s and CFU-c) present in mouse bone marrow. HLCM has poor colony stimulating activity in semi-solid cultures of mouse bone marrow cells, but invariably increases the number of colonies obtained in the presence of plateau levels of semi-purified colony stimulating factor (CSF). In liquid cultures, HLCM appears to contain a potent initiator of DNA synthesis in CFU-s, an activity which coincides with an increased CFU-s maintenance and causes a three- to four-fold increase in CFU-c number. It is apparent from this study that HLCM, in addition to stimulating colony formation in cultures of human bone marrow cells, has a profound in vitro effect on primitive haemopoietic progenitor cells of the mouse, which cannot be attributed to CSF.     

A colony-stimulating factor for neutrophil granulocytes: a marked increase of its production by the addition of sodium butyrate and lipopolysaccharide in serum-free culture of RSP-2 X P3 cells

Sodium butyrate, lithium acetate, and hydroxyurea given to serum-free culture of RSP-2 X P3 cells notably reduced the rate of cell proliferation but markedly enhanced the production of such a colony-stimulating factor (CSF) as one that stimulated predominantly neutrophilic granulocyte colony formation in mouse bone marrow cell cultures (Tsuneoka and Shikita, 1984). On the other hand, the production of macrophage CSF was not increased in the butyrate-treated RSP-2 X 3 cells. Butyrate also failed to enhance either macrophage CSF or neutrophil CSF production in L X P3 (mouse fibroblast line), Huk-1 X P3 (human kidney cell line) or Nil2C2 (hamster embryo fibroblast line) cells. The addition of bacterial lipopolysaccharide (LPS) together with butyrate resulted in further pronounced enhancement of the neutrophil CSF production in RSP-2 X P3 cells, while the cells did not develop tolerance against LPS upon repeated challenge. The yield of neutrophil CSF was thus increased by about 45 times that of the control during continuous culture for 12 days. Large-scale culture of the cells under these conditions must be an excellent source of a CSF for neutrophil granulocytes.     

Synergistic effects of purified recombinant human and murine B cell growth factor-1/IL-4 on colony formation in vitro by hematopoietic progenitor cells. Multiple actions

Purified recombinant human B cell growth factor-1/IL-4 was evaluated, alone and in combination, with purified preparations of recombinant human (rhu) CSF or erythropoietin (Epo) for effects on colony formation by human bone marrow CFU-GM progenitor cells (GM) and burst forming unit-E progenitor cells. rhu IL-4 synergized with rhu G-CSF to enhance granulocyte colony formation, but had no effect on CFU-GM colony formation stimulated by rhu GM-CSF, rhu IL-3, or rhu CSF-1. Rhu IL-4 synergized with Epo to enhance BFU-E colony formation equal to that of Epo plus either rhu IL-3, rhu GM-CSF, or rhu G-CSF. Removal of adherent cells and T lymphocytes did not influence the synergistic activities of rhu IL-4. Rmu IL-4, synergized with rhu G-CSF, but not with rmu GM-CSF, rmu IL-3, or natural mu CSF-1, to enhance CFU-GM (mainly granulocyte) colony numbers by a greater than 90% pure preparation of murine CFU-GM. Also, rhu IL-4 at low concentrations enhanced release of CSF and at higher concentrations the release also of suppressor molecules from human monocytes and PHA-stimulated human T lymphocytes. Use of specific CSF antibodies suggested that rhu IL-4 was enhancing the release of G-CSF and CSF-1 from monocytes and the release of GM-CSF and possibly G-CSF from PHA-stimulated T lymphocytes. Use of antibodies for TNF-alpha, IFN-gamma, or TNF-beta as well as measurement of TNF and IFN titers suggested that the suppressor molecule(s) released from monocytes were acting with TNF-alpha and those released from PHA-stimulated T lymphocytes were acting with IFN-gamma. These results implicate B cell growth factor-1/IL-4 as a synergistic activity for hematopoietic progenitors and suggest that the actions can be on both progenitor and accessory cells.     

The nature of 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated hemopoiesis, colony stimulating factor (CSF) requirement for colony formation, and the effect of TPA on [125I]CSF-1 binding to macrophages

The tumor-promoting phorbol diester, 12-O-tetradecanoylphorbol-13-acetate (TPA) was found to act both independently of and synergistically with the mononuclear phagocyte specific colony stimulating factor (CSF-1) to stimulate the formation of macrophage colonies in cultures of mouse bone marrow cells. In contrast, TPA did not synergize with other CSF subclasses that stimulate the formation of eosinophil, eosinophil-neutrophil, neutrophil, neutrophil-macrophage, and macrophage colonies, nor with either of the two factors required for megakaryocyte colony formation, megakaryocyte CSF, and megakaryocyte colony potentiator. In serum-free mouse bone marrow cell cultures TPA retained the ability to independently stimulate macrophage colony formation. However, TPA-stimulated colony formation was suboptimal and delayed in serum-free cultures that could support optimal colony formation in the presence of CSF-1. In addition, TPA did not directly compete with [125I]CSF-1 at 4 degrees C for its specific, high-affinity receptor on mouse peritoneal exudate macrophages. However, a 2-hour preincubation of the cells with TPA at 37 degrees caused almost complete loss of the receptor. Thus, TPA is able to mimic CSF-1 in its effects on CSF-1 responsive cells in some aspects (the spectrum of target cells, the morphology of resulting colonies, and the ability to down-regulate the CSF-1 receptor) but it is not able to mimic CSF-1 in other ways (TPA alone cannot stimulate the full CSF-1 response, TPA does not stimulate the most primitive CSF-1 responsive cells, and TPA does not bind to the CSF-1 receptor).     

Lithium selectively increases neuronal differentiation of hippocampal neural progenitor cells both in vitro and in vivo

Lithium has been demonstrated to increase neurogenesis in the dentate gyrus of rodent hippocampus. The present study was undertaken to investigate the effects of lithium on the proliferation and differentiation of rat neural progenitor cells in hippocampus both in vitro and in vivo. Lithium chloride (1-3 mM) produced a significant increase in the number of bromodeoxyuridine (BrdU)-positive cells in high-density cultures, but did not increase clonal size in low-density cultures. Lithium chloride at 1 mM (within the therapeutic range) also increased the number of cells double-labeled with BrdU antibody and TuJ1 (a class III beta-tubulin antibody) in high-density cultures and the number of TuJ1-positive cells in a clone of low-density cultures, whereas it decreased the number of glial fibrillary acidic protein-positive cells in both cultures. These results suggest that lithium selectively increased differentiation of neuronal progenitors. These actions of lithium appeared to enhance a neuronal subtype, calbindin(D28k)-positive cells, and involved a phosphorylated extracellular signal-regulated kinase and phosphorylated cyclic AMP response element-binding protein-dependent pathway both in vitro and in vivo. These findings suggest that lithium in therapeutic amounts may elicit its beneficial effects via facilitation of neural progenitor differentiation toward a calbindin(D28k)-positive neuronal cell type.     

高浓度葡萄糖对昆明小鼠早期胚胎发育的影响

建立昆明小鼠受孕模型,分离并体外培养胚胎细胞.检测了各培养浓度下的细胞增殖、分化与凋亡.胚胎细胞在0.2mmol/L和5.56mmol/L葡萄糖浓度的KSOM培养基中能正常发育和孵化;而在浓度为15.56mmol/L和25.56mmol/L葡萄糖培养基中胚胎发育和孵化均受到损害(P<0.005),且总细胞数和内细胞团细胞数也明显减少(P<0.01),但其细胞凋亡率与0.2mmol/L和5.56mmol/L葡萄糖浓度下胚胎细胞凋亡率无显著性差异(P>0.05).随着葡萄糖浓度的增高,胚泡总的表面积无明显变化,但胚胎细胞密度呈增加趋势.高血糖对早期胚胎的发育具有毒性作用,提示高糖可能导致妊娠合并糖尿病患者的流产和胎儿畸形率升高.     

Plasma and erythrocyte choline concentrations in rats following chronic treatment with lithium or choline

Rats were given daily injections of choline, lithium or lithium plus choline for either 11 or 18 days and red cell choline, glycine and glutathione levels were measured using proton nuclear magnetic resonance spectroscopy. In addition, plasma choline, plasma lithium and red cell lithium levels were measured 4 hr after the last dosage. Choline (1 mmol/kg) alone increased plasma but not red cell choline concentrations. Lithium (0.94 mmol/kg) elevated red cell choline levels but did not affect plasma choline concentrations. In contrast, red cell choline levels were not elevated in rats treated with a higher dose of lithium (1.88 mmol/kg). When choline was given in addition to the lower dose of lithium, a similar accumulation of red cell choline was observed suggesting that the lithium-induced choline accumulation was not enhanced by a greater availability of free choline. No differences were detected in red cell glycine or glutathione levels between any of the treatment groups. Therefore, lithium produced a specific (dose-dependent) accumulation of choline in rat erythrocytes. However, the 100% increase observed in rats was not as marked as the increased red cell choline levels reported in patients maintained on lithium (8 to 10-fold). This discrepancy supports the concept that species differences exist in red cell choline transport or metabolism.     

Migration inhibitory action of bacterial lipopolysaccharide on progenitor cells of monocyte/macrophage lineage growing in culture in the presence of colony-stimulating factor (CSF-1)

Addition of lipopolysaccharide (LPS) to the culture of mouse myeloid stem cells (CFU_c) increased the incidence of compact colonies and decreased that of dispersed ones in the presence of colony-stimulating factor (CSF-1) which had not such an effect by itself even in high concentrations. Although colony morphology was thus changed, nearly all colonies were composed of monocytes. The incidence of compact colonies increased with the increase of LPS concentration but plateaued at about 50%. Bone marrow cells of LPS-tolerant mice responded to LPS in vitro to a slightly decreased extent. The activity of LPS was decreased by alkaline or acid hydrolysis of the LPS molecule and inhibited by polymixin B, but not by indomethacin, α-L-fucose, nor by α-methyl-D-mannoside. Other immunopotentiating substances, such as OK-432, Lentinan, and Levamisole, had no effect on the colony morphology. Both muramyl dipeptide and poly(I)poly(C) were also ineffective. Furthermore, the action of LPS was not abolished by the use of heat-inactivated serum in the culture. LPS was no longer stimulative for the induction of lysosomal enzymes in the CSF-stimulated culture, although it greatly enhanced the enzyme induction in the unstimulated culture. These results indicate that the cells of monocyte/macrophage lineage develop the capacity for migration before they become responsive to LPS, and that the LPS-responding monocytic cells can proliferate even in a state of confluence induced by LPS.     

Effects of lithium and insulin on glycogen synthesis in L6 myocytes: additive effects on inactivation of glycogen synthase kinase-3

In insulin-sensitive L6 myocytes, insulin stimulated glycogen synthesis in a dose-dependent manner and lithium further stimulated glycogen synthesis at all insulin concentrations. Lithium alone at 20 mM stimulated glycogen synthesis to the degree similar to the maximal insulin response. Effects of lithium and insulin were fully additive for both glycogen synthesis and glycogen synthase activity. In L6 myocytes, insulin increased phosphorylation of Akt1 and glycogen synthase kinase-3 alpha and beta (GSK-3 alpha and beta), resulting in its activation and inactivation, respectively. Unlike insulin, lithium directly inhibited GSK-3 (both alpha and beta) without affecting phosphorylation of GSK-3. Moreover, lithium in vitro could further inhibit enzyme activity of GSK-3 (both alpha and beta) that was isolated from insulin-stimulated cells (thus already phosphorylated and inactivated by insulin). In summary, insulin increases glycogen synthesis by the Akt1/GSK-3/glycogen synthase pathway, but lithium increases glycogen synthesis by direct inhibition of GSK-3 in L6 myocytes. Inhibitory effects of lithium and insulin on GSK-3 (both alpha and beta) were additive, which may account, at least in part, for their additive effects on glycogen synthase activity and glycogen synthesis in L6 myocytes.     

Studies on colony formation in vitro by mouse bone marrow cells. II. Action of colony stimulating factor

An analysis was made of some of the processes involved in the stimulation by colony stimulating factor (CSF) of cluster and colony formation by mouse bone marrow cells in agar cultures in vitro. Colony formation was shown to be related to the concentration and not the total amount of CSF. The concentration of CSF determined the rate of new cluster initiation in cultures and the rate of growth of individual clusters. Colony growth depleted the medium of CSF suggesting that colony cells may utilise CSF during proliferation. Bone marrow cells incubated in agar in the absence of CSF rapidly died or lost their capacity to proliferate and form clusters or colonies. CSF appears (a) to be necessary for survival of cluster-and colony-forming cells or for survival of their proliferative potential, (b) to shorten the lag period before individual cells commence proliferation and (c) to increase the growth rate of individual clusters and colonies.     

Induction of colony-stimulating factors by Plasmodium cynomolgi components

Plasmodium cynomolgi total parasite antigens soluble in culture medium (P.c.SA), when injected in monkeys (Macaca mulatta) intravenously, induced the synthesis and secretion of serum colony-stimulating factors (CSFs). In vitro cultured monkey splenic macrophages and blood monocytes, following incubation with P.c.SA, also elaborated CSFs: the splenic macrophages responded more. Peak CSFs levels, both in vivo and in vitro, were attained after 8 hours of P.c.SA stimulation, and thereafter declined to baseline values within 48 hours. CSFs, both in serum and in conditioned medium, induced the formation of macrophage, granulocyte and granulocyte-macrophage colonies in vitro, in the same proportion, indicating that committed progenitor cells responded to CSF from both sources in a similar way. Polymyxin B treatment had no effect on P.c.SA stimulated CSF elaboration by macrophages, suggesting an LPS-independent mechanism of CSF induction. CSF synthesis appeared to be de novo, as cycloheximide treatment of macrophages completely inhibited CSF production. These observations indicate that P. cynomolgi components can induce CSF synthesis.     

Regulation of inositol monophosphatase in Saccharomyces cerevisiae

Inositol monophosphatase is a key enzyme in the de novo biosynthesis of inositol and in the phosphoinositide second-messenger signalling pathway. Inhibition of this enzyme is a proposed mechanism for lithium's pharmacological action in bipolar illness (manic depression). Very little is known about how expression of this enzyme is regulated. Because the yeast Saccharomyces cerevisiae has been shown to be an excellent model system in which to understand the regulation of inositol metabolism, we characterized inositol monophosphatase in this yeast. Lithium inhibited monophosphatase activity in vitro . Growth in the presence of inositol resulted in increased expression of the enzyme in vivo , although inositol had no effect on enzyme activity in vitro . The inositol effect was apparent when cells were grown in glucose but not in glycerol/ethanol. Monophosphatase activity was derepressed as cells entered stationary phase. This effect was apparent only during growth in glucose plus inositol. The results demonstrate that S. cerevisiae monophosphatase is inhibited by lithium and regulated by factors affecting phospholipid biosynthesis.     

Lithium increases expression of p21WAF/Cip1 and survivin in human glioblastoma cells

Lithium is the most widely prescribed mood stabilizer, but the precise molecular mechanisms underlying its therapeutic function are not yet fully elucidated. Recent preclinical and clinical evidence indicates its neuroprotective and neurotrophic effects. As a tight coupling of function and metabolism in the central nervous system between glial cells and neurons has recently been detected, lithium's effect on glial cells may participate also in the total beneficial effects of this drug. The aim of the present study was to analyze molecular mechanisms induced in human glioblastoma A1235 cells by the treatment with lithium, especially its influence on the expression of apoptosis-related genes. Lower levels of lithium (0.5 mmol/L and 2 mmol/L) did not cause any cytotoxicity or changes in the cell cycle phase distribution following 72 h incubation. However, a higher dose (20 mmol/L) was cytostatic for glioblastoma cells, and caused accumulation of cells in G₂/M phase of the cell cycle. The treatment with lithium did not alter the levels of Bcl-2 or procaspase-3 and did not cleave PARP, but increased the levels of p21^WAF/Cip1 and survivin. Thus, increased expression of p21^WAF/Cip1 (a protein with antiapoptotic function), and survivin (a protein that supports the growth of cells by suppression of apoptosis and promotion of cell proliferation) may be the early events in the long-term cell response to lithium that are involved in the beneficial effects of this drug.     

Effects of lithium on the hypothalamo-pituitary-adrenal axis

The effect of lithium on the hypothalamo-pituitary-adrenal axis was studied in vivo and in vitro. The levels of plasma vasopressin, ACTH and corticosterone increased after the administration of lithium (LiCl 4 mmol/kg BW, 11 days) in rats, while the tissue vasopressin concentration in the median eminence, the rest of the hypothalamus and the posterior pituitary was decreased. The CRF concentration in the posterior pituitary increased markedly, but it did not change significantly in the median eminence or the rest of the hypothalamus. The elevated plasma ACTH level might be at least partly due to the increased vasopression secretion. Lithium stimulated ACTH secretion per se and also enhanced vasopressin-induced ACTH secretion in cultured pituitary cells and in half pituitary incubations, while it did not affect CRF-induced ACTH secretion. Lithium inhibited CRF-induced cAMP accumulation in half pituitary incubations, while lithium and vasopressin did not affect cAMP accumulation per se or even when administered together. The results suggest that lithium-induced ACTH release is via a cAMP-independent mechanism. Thus, it is possible that lithium stimulates ACTH release by acting directly on the corticotroph, stimulating vasopressin release and potentiating vasopressin-induced ACTH release.     

The influence of Li+ ions on pepsin and trypsin activity in vitro

BackgroundThe paper presents a study on the influence of different lithium carbonate and lithium citrate concentration on proteolytic enzymes, namely pepsin and trypsin, in vitro. Lithium can directly affect enzyme activity. Its influence on many bodily functions in both ill and healthy people has been proven.MethodsTo assess the influence of Li⁺ ions concentration and the substrate/enzyme ratio on pepsin and trypsin activity in vitro, 60 factorial experiments were conducted (each repeated 30 times).Main findingsFor both enzymes, statistically significant changes in their activity under the influence of lihium carbonate and lithium citrate were observed. The biggest increase in enzyme activity reached even 198.6 % and the largest decrease in enzyme activity reached about 50 %.ConclusionsThe study shows that both organic and inorganic forms of lithium salts cause changes in the activity of digestive enzymes. Different concentrations of lithium carbonate and lithium citrate stimulate or inhibit the activity of trypsin and pepsin.