c-Jun, the most extensively studied protein of the activator protein-1 (AP-1) complex, is involved in numerous cell activities, such as proliferation, apoptosis, survival, tumorigenesis and tissue morphogenesis. Earlier studies focused on the structure and function have led to the identification of c-Jun as a basic leucine zipper (bZIP) transcription factor that acts as homo- or heterodimer, binding to DNA and regulating gene transcription. Later on, it was shown that extracellular signals can induce post-translational modifications of c-Jun, resulting in altered transcriptional activity and target gene expression. More recent work has uncovered multiple layers of a complex regulatory scheme in which c-Jun is able to crosstalk, amplify and integrate different signals for tissue development and disease. One example of such scheme is the autocrine amplification loop, in which signal-induced AP-1 activates the c-Jun gene promoter, while increased c-Jun expression feedbacks to potentiate AP-1 activity. Another example of such scheme, based on recent characterization of gene knockout mice, is that c-Jun integrates signals of several developmental pathways, including EGFR-ERK, EGFR-RhoA-ROCK, and activin B-MAP3K1-JNK for embryonic eyelid closure. After more than two decades of extensive research, c-Jun remains at the center stage of a molecular network with mysterious functional properties, some of which are yet to be discovered. In this article, we will provide a brief historical overview of studies on c-Jun regulation and function, and use eyelid development as an example to illustrate the complexity of c-Jun crosstalking with signaling pathways.
Animals ; Humans ; Mice ; Proto-Oncogene Proteins c-jun ; genetics ; metabolism ; Signal Transduction

OBJECTIVETo study the effect of selenium (Se) and iodine (I) and the compound of both on the proto-oncogenes c-fos and c-jun mRNA and their protein expression in the cultured rat hippocampus neurons.

METHODSUsing the technique of serum free hippocampus neuron culture, different doses of Se and I and Se + I compound were added into the medium. The expression of the mRNA of c-fos, c-jun in hippocampus neurons cultured for 1, 3, 5, 7 and 10 d were studied using both in situ hybridization and SABC immunohistochemical technique.

RESULTSBoth Se and I could enhance the expression of c-fos, c-jun mRNA and their proteins, especially the combination of I and Se able to give a remarkable effect on c-jun mRNA expression.

CONCLUSIONSSe and I may effect the expression of both c-fos and c-jun mRNA, especially the c-jun mRNA and its protein of hippocampus neurons, and thus may effect the differentiation and development of neurons.

Animals ; DNA-Binding Proteins ; metabolism ; Hippocampus ; metabolism ; Iodine ; Neurons ; metabolism ; Proto-Oncogene Proteins c-fos ; metabolism ; Proto-Oncogene Proteins c-jun ; metabolism ; RNA, Messenger ; metabolism ; Rats ; Selenium

OBJECTIVETo observe activating protein-1 (AP- 1) members in response to changes of wall-shear stress in osteoblastic cells in vitro.

METHODSIsolated and purified osteoblastic cells from the calvaria of newborn SD rats were cultured and subcultured. The third generation cells were subjected to wall-shear stress of 0.8 Pa, 1.2 Pa, 1.4 Pa and 1.6 Pa separately. Gene expression of the seven AP-1 members were studied before (0 h) and 10 min, 15 min, 30 min, 60 min after treated with wall-shear stress.

RESULTSThe expression of FosB, c-Fos, c-Jun, JunD and JunB mRNA increased transiently after application of 1.2 Pa wall-shear stress in osteoblastic cells compared to 0.8 Pa , 1.4 Pa and 1.6 Pa stress, and peaked at 15 min.

CONCLUSIONMechanical environment changes in osteoblastic cells induced a dramatic induction of most of the AP-1 members.

Animals ; Proto-Oncogene Proteins c-fos ; Proto-Oncogene Proteins c-jun ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Stress, Mechanical ; Transcription Factor AP-1

BACKGROUNDA new brain region, the marginal division (MrD), was discovered at the caudal margin of the neostriatum. The MrD was shown to be involved in learning and memory in the rat. The aim of this study was to investigate the expression of the immediate-early genes c-fos and c-jun in the MrD of the striatum during learning and memory processes in the rat, immunocytochemical and Western blot methods were used to examine Y-maze trained rats.

METHODSThe rats were divided into three groups, namely the training, pseudotraining, and control groups. After Y-maze training, the expression of the immediate-early genes c-fos and c-jun in the MrD of the rats was investigated using immunocytochemical and Western blot methods.

RESULTSAfter one hour of Y-maze training, the expression of c-jun and c-fos proteins was significantly enhanced in the MrD; the c-jun protein, in particular, was more intensely expressed in this region than in other parts of the striatum. The expression of these two proteins in the training group was significantly higher than in the pseudotraining and control groups. In addition, positive expression was also found in the hippocampus, cingulum cortex, thalamus, and in other areas. Western blot disclosed two immunoreactive bands for the anti-c-fos antibody (47 kD and 54 kD) and two immunoreactive bands for the anti-c-jun antibody (39 kD and 54 kD).

CONCLUSIONSThese results indicate that the immediate-early genes c-fos and c-jun participate in signal transduction during the learning and memory processes associated with Y-maze training in rats.

Animals ; Male ; Maze Learning ; Memory ; Neostriatum ; metabolism ; Proto-Oncogene Proteins c-fos ; biosynthesis ; Proto-Oncogene Proteins c-jun ; biosynthesis ; Rats ; Rats, Sprague-Dawley

Apoptosis ; Cell Cycle ; Cell Differentiation ; Cell Proliferation ; Humans ; Neoplastic Processes ; Proto-Oncogene Proteins c-jun ; genetics ; metabolism ; physiology

OBJECTIVE: To study the effect of forsythiaside on the expression of c-jun induced by cisplatin in the cochlea of guinea pig. METHOD: Thirty guinea pigs were randomly divided into control group (10), cisplatin group (10) and forsythiaside group (10). The ototoxicity model was done with intraperitoneal injection of cisplatin solution (8 mg/kg per day) for 7 days. Forsythiaside (25 mg/kg per day) was injected 30 min before cisplatin solution treated in guinea pigs of forsythiaside group for 7 consecutive days. The saline instead of cisplatin was injected in normal control group. The distortion product otoacoustic emission (DPOAE) was detected before animals were killed. The expression of c-jun in cochlea of guinea pigs was detected by western blotting. The expression of c-jun mRNA in cochlea of guinea pigs was detected by reverse transcriptase polymerase chain reaction (RT-PCR). RESULT: DPOAE amplitudes in cisplatin group was significantly lower than in control group (P < 0.01). Compared with cisplatin group, DPOAE amplitudes in forsythiaside group was increased significantly (P < 0.05). The expression of c-jun protein and mRNA were significantly increased in cisplatin group than in control group (P < 0.01). Compared with cisplatin group, the expression of c-jun protein and mRNA were significantly decreased in forsythiaside group. CONCLUSION Forsythiaside can significantly reduce the side effects induced by cisplatin through down-regulating the expression of c-jun.
Animals ; Cisplatin ; toxicity ; Cochlea ; drug effects ; metabolism ; Female ; Glycosides ; pharmacology ; Guinea Pigs ; Male ; Proto-Oncogene Proteins c-jun ; metabolism

OBJECTIVETo study the effects of VAC on starting the process of wound healing and decreasing apoptosis.

METHODSTo examine the variations in expression of proto-oncogenes c-myc, c-jun and Bcl-2 in pig wound model with acute full-thickness skin defect and human chronic wounds by immunohistochemistry, calculate the numbers of expressive positive cells and the labelling index (LI), and observe the process of wound healing.

RESULTS(1) In pig experiment, the wound in experimental group was very clean and without obvious exudates, many neoepiderm and granulation tissue rapidly appeared or formed after 6 days, and healed completely by the 25th day. On the contrary, in the wound of control group, more exudates and blood crust could be seen and fewer neoepiderm and granulation tissue appeared after 6 days and was healed by 30th day. Immediately after the wound was created, the expression of c-myc, c-jun and Bcl-2 was lower and mainly situated in nucleus or cytoplasma of the basilar cells. After the wound was created in control group, or after starting the VAC treatment in experimental group, their expression rapidly and obviously increased, the distribution of the positive cells also became enlarged, but the amount of expression decreased rapidly after the expressive peak have reached. In the successive 12 days following the wound was created, the expression of c-myc, c-jun and Bcl-2 in the experimental group was constantly higher than that of the control group. (2) In human chronic wounds, there wasn't obvious secretions and more healthy granulation tissue was rapidly formed after VAC treatment. The expression of c-jun was mainly located in cytoplasma of basilar cells of epithelium, dermal fibroblasts and inflammatory cells, and the positive cell and labelling index obviously decreased. The expression of c-myc and Bcl-2 was mainly in cytoplasma of basilar cells, but the amount of expression and the labelling index became obviously increased after VAC treatment.

CONCLUSIONSVAC could rapidly start the healing course of the pig' s acute skin wound and human chronic wound, decrease apoptosis of the reparative cells, so as to accelerate wound healing.

Adult ; Animals ; Apoptosis ; Female ; Humans ; Male ; Middle Aged ; Negative-Pressure Wound Therapy ; Proto-Oncogene Proteins c-jun ; metabolism ; Proto-Oncogenes ; Swine ; Wound Healing

OBJECTIVETo explore the molecular mechanism of brain protection against convulsive brain damage in premature brains by observing the changes of apoptotic-regulating genes of bcl-2 and c-Jun expression in the hippocampus in Wistar rats with different ages after status convulsion (SC).

METHODSSC was induced in infant Wistar rats (IRs) and adult Wistar rats (ARs) by intraperitoneal injection of lithium-pilocarpine. The rats were sacrificed at 3 hrs, 6 hrs, 12 hrs, 1 day, 3 days and 7 days after SC (n=8). Bcl-2 and c-Jun protein and mRNA levels were measured using immunocytochemistry, RT-PCR and in situ hybridization.

RESULTSc-Jun protein levels increased significantly at 3 hrs and reached the peak at 6 hrs after SC in both IRs and ARs compared to those in the normal control group (P<0.01). c-Jun protein levels started to decrease 12 hrs after SC in both IRs and ARs. The expression of c-Jun protein in IRs returned to the basal level 1 day after SC, while remained higher in ARs than in the normal control group by 7 days after SC. The expression of c-Jun protein in ARs was much higher than that in IRs from 6 hrs to 7 days after SC (P<0.05). c-Jun mRNA level was in parallel with the protein level as mentioned in IRs and ARs after SC. There were no changes observed in both bcl-2 protein and bcl-2 mRNA levels after SC in IRs and ARs.

CONCLUSIONSSC may induce an up-regulation of proapoptotic gene c-Jun in the hippocampus after SC, with a less strong extent and shorter duration in IRs compared to that in ARs. This might be one mechanism of brain protection against convulsive brain damage in IRs. The expression of bcl-2 remains unchanged after SC and is not affected by age in both IRs and ARs.

Animals ; Apoptosis ; Gene Expression Regulation ; Hippocampus ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; analysis ; genetics ; Proto-Oncogene Proteins c-jun ; analysis ; genetics ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; Seizures ; metabolism

OBJECTIVETo study the potential relationship between the expressions of c-jun and c-fos oncogenes and the prognosis of medulloblastoma.

METHODSThe specimens from 70 cases of medulloblastoma of the posterior fossa and 10 cases of normal cerebellar tissues were collected to determine c-jun and c-fos expressions by immunohistochemical staining in formalin fixed paraffin-embedded sections.

RESULTS(1) It showed that c-fos and c-jun protein expression was negative in 10 normal cerebellar tissue, while positive c-fos, c-jun immunoreactivity was found in 70 medulloblastoma specimens. The positive rate of c-jun and c-fos was 80% and 77%, respectively. There was high expression of c-jun and c-fos protein in medulloblastoma tissues. (2) There were positive correlations and strong co-operativity between c-jun and c-fos expression (r = 0.493, P < 0.01). (3) Correlative analysis indicated that expression of c-jun, c-fos were significantly correlated with survival time (c-jun: r = -0.447, P < 0.01; c-fos: r = -0.590, P < 0.01). The higher the expression level of c-jun and c-fos protein was, the worse the prognosis was in medulloblastoma patients.

CONCLUSIONSHigh expression of c-jun and c-fos protein could be noted in medulloblastoma tissues. The two transcription factors show positive correlation and strong co-existence between c-jun and c-fos expressions. The expression levels of c-jun as well as c-fos are negatively correlated with the mortality rate and life expectancy of patients with medulloblastoma. In addition, the co-expression of c-jun and c-fos could serve as an indicator for judging the prognosis of medulloblastoma.

Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Humans ; Immunohistochemistry ; Infant ; Male ; Medulloblastoma ; metabolism ; mortality ; pathology ; Proto-Oncogene Proteins c-fos ; analysis ; Proto-Oncogene Proteins c-jun ; analysis ; Survival Analysis ; Survival Rate

OBJECTIVETo explore the DNA damage and the expression of oncogenic protein induced by cadmium in vitro (human cells) and in vivo in rats.

METHODSThe colony formation assay and the MTT assay were employed to determine the cytotoxicity of cadmium. The DNA damage and the cell cycle were measured by the comet assay and the flow cytometry, respectively. The western bolt and the X-Gal staining were also used to determine the change of oncogenic protein and the senescent marker.

RESULTSThe cadmium inhibited the proliferation of cells and induced DNA damage significantly not only in human cultured cells but also in vivo animal cells. The comet rate increased from 6.1% in the control group to 23.2% in 200 microM cadmium treatment group (P < 0.01). The comet rate increased in all organs of male rats with the increase of dosage, and there were significant difference between treatment the groups and the control group in kidney and ventral prostate (P < 0.05). Furthermore, the cadmium blocked the cell cycle progression. At the same time, the expression of c-myc, c-Jun and beta-Gal were increased by cadmium.

CONCLUSIONThe cadmium could induce DNA damage and block the cell cycle, and further cause senescence, and death. However, the cadmium induced the DNA damage and the oncogenic protein expression may be the important factors to cause cancer.

Animals ; Cadmium ; toxicity ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Comet Assay ; DNA ; drug effects ; DNA Damage ; Dose-Response Relationship, Drug ; Male ; Proto-Oncogene Proteins c-fos ; biosynthesis ; Proto-Oncogene Proteins c-jun ; biosynthesis ; Rats ; Rats, Wistar