OBJECTIVETo explore the mechanism of neurotoxicity induced by manganese, and observe the effects on the apoptosis of neurons in rat striatum.

METHODSSD rats were divided into four groups, six rats each group. Three dose groups were exposed to high, middle, and low level of MnCl(2). At the end of experiment, all rats of the exposed groups and control group were decapitated, their striatums were removed and the Mn content of striatum, the apoptotic morphology, ratio and ultrastructural organization were analyzed.

RESULTSThe Mn content of striatum and apoptosis index of the three dose groups exposed to high, middle, and low level of Mn were significantly higher than control group (P < 0.05). The Mn content of striatum of the three dose groups exposed to high, middle, low level of MnCl(2) and control group were 2.98 +/- 0.52, 2.75 +/- 0.37, 2.61 +/- 0.73, 0.60 +/- 0.20 respectively. The apoptosis index of striatum of the three dose groups exposed to high, middle, low level of MnCl(2) and control group were 24.83 +/- 5.98, 17.00 +/- 5.33, 15.33 +/- 2.58, 2.83 +/- 0.41 respectively, and following higher level dose, the apoptosis index increased. The nucleus of neurons in striatum become smaller, condensed, etc, and these character showed apoptosis of neurons.

CONCLUSIONMn can result in apoptotic morphology and increase level of apoptosis in striatum. The level of apoptos varies with Mn concentration.

Animals ; Apoptosis ; drug effects ; Corpus Striatum ; drug effects ; Manganese ; Neurons ; drug effects ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate the effects of Bisnaphthalimide (C8) on the proliferation and apoptosis of SMMC-7721 cells.

METHODSThe effects of C8 on the proliferation of SMMC-7721 cells were evaluated by MTT. Cell cycle and apoptotic cell percentage were studied by flow cytometry. The protein of Bcl-2 was detected by Western blot. The intra-cellular protein of Bcl-2 was detected by flow cytometry. The proteins of caspase9 and caspase3 were detected by ELISA.

RESULTSC8 inhibited the growth of SMMC-7721 cells. The IC50 of C8 on SMMC-7721 cells was 15 micromol/L. C8 initiated apoptosis of SMMC-7721 cells. After SMMC-7721 cells were exposed to C8 in concentrations of 10, 15, 20 micromol/L, the apoptosis rates were 16.8%, 29.4% and 35.8%, respectively, significantly higher than those of the controls (P less than 0.01). Flow cytometry and Western blot analysis showed that Bcl-2 protein level was inhibited after treatment with C8. The ELISA analysis showed that caspase9 and caspase3 were activated in the SMMC-7721 cells after the C8 treatment.

CONCLUSIONC8 could induce apoptosis of human liver cancer SMMC-7721 cells. C8 might be a potential efficient anticancer drug.

Apoptosis ; drug effects ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; drug effects ; Humans ; Naphthalimides ; pharmacology

Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Humans ; K562 Cells ; drug effects ; Phloretin ; pharmacology

OBJECTIVETo investigate the effects of activated AKT on murine myeloid precursor cells (32D cells), and the effects of IFN-γ on 32D cells and its mechanisms.

METHODSPlasmid transduction was used to enhance the expression of AKT on 32D cells. After the transfected cells treated with IFN-γ for 24 hours, proliferation rate was tested by WST-1, apoptosis by flow cytometry, expression of phosphorylated Erk1/2, Stat3 and phosphorylated Stat3 was determined by Western blot.

RESULTS(1) IFN-γ at low concentration (100 U/ml) enhanced the growth and proliferation of 32D cells, while at high concentration (1000 U/ml) suppressed them. (2) Compared with control groups, low concentration IFN-γ increased (1124 ± 13) Stat3 phosphorylation in 32D-cell, while it high concentration IFN-γ decreased (601 ± 13). 32D cells transfected with activated Akt grew rapidly (0.287 ± 0.010) and had a low apoptotic rate [(9.57 ± 0.17)% (P < 0.05)]. (3) The expression of p-Erk1/2 in transfected 32D-cell was significantly reduced (P < 0.05). (4) Apoptosis rate of IFN-γ treated group was significantly decreased in transfected 32D cells (P < 0.05).

CONCLUSIONSIFN-γ has dual effects on 32D cells, namely, at low concentration enhanced the growth and proliferation of 32D cells, while at high concentration suppressed them. Its mechanisims is possibly through Stat3 pathway. Activated Akt can significantly promote the growth and proliferation of 32D cell and significantly inhibit apoptosis and IFN-γ can regulate cell proliferation and apoptosis through AKT. AKT activation can inhibit the Erk signal pathway, which may be affected by inhibition the modificaton of Raf1.

Animals ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Phosphorylation ; drug effects ; STAT3 Transcription Factor ; metabolism ; Signal Transduction ; drug effects

All-trans retinoic acid (ATRA) is a vitamin A derivative and plays an important role in the regulation of cell aggregation, differentiation, apoptosis, proliferation, and inflammatory response. In recent years, some progress has been made in the role of ATRA in renal diseases, especially its protective effect on podocytes. This article reviews the research advances in podocyte injury, characteristics of ATRA, podocyte differentiation and regeneration induced by ATRA, and the protective effect of ATRA against proliferation, deposition of fibers, and apoptosis.
Apoptosis ; drug effects ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Cytoprotection ; Humans ; Podocytes ; drug effects ; physiology ; Tretinoin ; pharmacology

OBJECTIVETo explore the effect of exogenous putrescine on renal function and cell apoptosis in rats.

METHODSNinety SD rats were randomized into control group (n=10), high-dose putrescine group (P1 group, n=40), and low-dose putrescine group (P2 group, n=40) with intraperitoneal injections of 2 ml of normal saline, 50 µg/g putrescine, and 25 µg/g putrescine, respectively. At 24, 48, 72 and 96 h after the injections, 10 rats from each group were sacrificed to examine serum Cr and BUN levels, histological changes in the kidneys, and renal cell apoptosis (TUNEL assay).

RESULTSThe rats in the two putrescine- treated groups showed mild edema in some renal tissues without obvious necrosis. In P1 and P2 groups, serum Cr and BUN levels differed significantly at each time point of measurement (P<0.01 and P<0.05, respectively), and were significantly higher than the levels in the control group (P<0.01 and P<0.05, respectively). The two putrescine-treated groups showed gradually increased renal cell apoptosis with time, reaching the peak levels at 96 h and 48 h, respectively. The peak renal cell apoptosis rates in P1 [(24.78∓2.19)%] and P2 [(26.27∓2.13)%] group were significantly higher than the rate in the control group [(4.47∓0.33)%, P<0.01].

CONCLUSIONExogenous putrescine can lead to renal function impairment and induce renal cell apoptosis in rats, and the severity of these changes appeared to be associated with the blood concentration of exogenous putrescine.

Animals ; Apoptosis ; drug effects ; Kidney ; drug effects ; physiopathology ; Putrescine ; adverse effects ; blood ; Rats ; Rats, Sprague-Dawley

Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Cell Line, Tumor ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Humans ; Oxides ; pharmacology ; Point Mutation

OBJECTIVETo investigate the protective effect of the tert-butylhydroquinone (tBHQ) on PC12 cells from neurotoxicity induced by manganese.

METHODSCytotoxicity of PC12 cells was measured by MTT assay, following the PC12 cells treatment with different concentrations of MnCl₂ (300, 600, 900 μmol/L) for 24, 48 or 72 h. PC12 cells were pretreated with 40 μmol/L tBHQ for 12 h, followed by the treatment of 600 micromol/L or 300 μmol/L MnCl₂ for 72 h. Cytotoxicity of PC12 cells was measured by MTT assay, and cell apoptosis was examined by the method of Annexin V-FITC/PI in flow cytometry (FCM).

RESULTSThe proliferation of PC12 cells treated with 300, 600, 900 μmol/L MnCl2 was suppressed in the dose dependent pattern (P < 0.01). Proliferation of PC12 cells treated with 600 μmol/L MnCl₂ was suppressed to 40% of that in control group (P < 0.01), but the proliferation rate of PC12 cell pretreated with 40 μmol/L tBHQ was 180% of that in control group (P < 0.01). Apoptotic rate of PC12 cells treated with 300 micromol/L MnCl₂ was higher than the vehicle control group (P < 0.01). Apoptotic rate of 40 μmol/L tBHQ pretreatment followed by 300 μmol/L MnCl₂ treatment was lower than that of MnCl2 treatment group (P < 0.01). The inhibition rate of apoptosis was 61%.

CONCLUSIONSManganese may suppress PC12 cells proliferation and induce apoptosis. tBHQ can reduce PC12 cells proliferation suppressed by manganese and attenuate the apoptosis induced by manganese.

Animals ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Drug Antagonism ; Hydroquinones ; pharmacology ; Manganese ; toxicity ; PC12 Cells ; drug effects ; Rats

No abstract available.
Animal ; Apoptosis/*drug effects ; Human ; Tumor Cells, Cultured

Apoptosis ; drug effects ; Asbestos ; toxicity ; Humans ; Mineral Fibers ; toxicity