OBJECTIVE: To explore the genetic basis of a patient with early-onset Parkinson disease from a consanguineous family. METHODS: Homozygosity mapping and Sanger sequencing of cDNA were used to identify the causative mutation. RESULTS: A homozygous missense variation (c.56C>G, p.Thr19Arg) in the PARK7 gene was identified in the patient. In silico analysis suggested the c.56C>G variation to be pathogenic. CONCLUSION Homozygous c.56C>G variation of the PARK7 gene was the disease-causing variation in this family.
Consanguinity ; Homozygote ; Humans ; Mutation, Missense ; Parkinson Disease ; genetics ; Pedigree ; Protein Deglycase DJ-1 ; genetics

Parkinson's disease (PD) is a neurodegenerative movement disorder mainly due to degeneration of dopaminergic neurons in the substantia nigra. Most PD cases are sporadic and only 5%-10% of patients carry mutations with inheritance. Among them, the mutation of DJ-1 is related to the autosomal recessive early-onset parkinsonism. DJ-1, the Parkinson's disease-related protein, plays important roles in different physiopathological processes, including oxidative stress, cell translocation and regulation of transcription and translation. DJ-1 is known to be widely expressed in different areas of brain, including hippocampus, amygdala, substantia nigra and cortical areas. Several researchers have tried to demonstrate the clinical and neuroimaging features of DJ-1 related parkinsonism. The DJ-1 knockout mouse model was established to further explore the mechanisms of different functions. Moreover, the search for different forms of DJ-1 as potential biomarkers of PD also provides guidance for its accurate diagnosis and treatment in the future.
Animals ; Dopaminergic Neurons ; Mice ; Oncogene Proteins ; Oxidative Stress ; Parkinson Disease ; Protein Deglycase DJ-1 ; Substantia Nigra

Multifunctional sperm protein 22 (SP22) is expressed ubiquitously and related to quite a few diseases. Located on the sperm surface, SP22 has an enzymatic activity that may assist sperm in penetrating into the ovum. SP22 may be carcinogenic in conspiracy with the factor ras. Among all species SP22 is highly conservative, which demonstrates its importance to life. More and more studies indicate that SP22 is directly correlated with male infertility and Parkinsons disease. This article summarizes recent researches on SP22 in the gene structure, protein structure and functional characteristics.
Animals ; Gene Components ; Humans ; Male ; Microtubule-Associated Proteins ; chemistry ; genetics ; physiology ; Protein Conformation ; Protein Deglycase DJ-1 ; Rats ; Spermatozoa ; physiology

OBJECTIVETo assess the effect of small interfering RNA (siRNA)-mediated gene silencing of DJ-1 on the proliferation of human laryngeal carcinoma cell line Hep-2.

METHODSThree siRNA sequences specific to DJ-1 gene were synthesized according to GenBank. Human laryngeal carcinoma cell line Hep-2 was cultured and divided into 4 groups: non-specific group (siRNA control) and 3 RNAi groups, transfected with specific DJ-1 siRNA (siRNA1, siRNA2, siRNA3). The mRNA and protein levels of DJ-1 were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot respectively. Cell apoptosis were analyzed by flow cytometry. The proliferation of Hep-2 cells was assessed by MTT assay.

RESULTSDJ-1 siRNA down-regulated the mRNA and protein levels of DJ-1 in Hep-2 cells. After transfection, the expression of DJ-1 mRNA and protein levels in Hep-2 cells of the DJ-1 siRNA1 group were significantly lower than those of non-specific siRNA control group. MTT assay showed that DJ-1 siRNA1 group inhibited proliferation of Hep-2 cells. Flow cytometry showed that apoptosis rate of the DJ-1 siRNA1 group (15.7%) was significantly higher than that of non-specific siRNA control group (4.5%) or untransfected group (3.5%), t = 4.736, P < 0.01.

CONCLUSIONSSpecific siRNA targeting DJ-1 can effectively inhibit DJ-1 expression, resulting in the reduced proliferation and the enhanced apoptosis in Hep-2 cells.

Cell Line, Tumor ; Cell Proliferation ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Laryngeal Neoplasms ; genetics ; pathology ; Oncogene Proteins ; genetics ; Protein Deglycase DJ-1 ; RNA Interference ; RNA, Messenger ; genetics ; RNA, Small Interfering ; genetics

OBJECTIVETo detect the expression of DJ-1 in laryngeal squamous cell carcinoma (LSCC) and to study the relationship between DJ-1 expression and clinical indexes of LSCC.

METHODSThe expressions of DJ-1 protein in 71 LSCC samples and 9 cases control samples from laryngeal mucosa tissues of non-LSCC patients were detected using streptavidin peroxidase immunohistochemistry staining and the relationships between DJ-1 protein expression and clinicopathologic characteristics were analyzed.

RESULTS(1) The positive expression rate of DJ-1 protein in LSCC was 85.9%(61/71), which was significantly higher than the rate (55.5%, 5/9) in control laryngeal mucosa tissues (P < 0.05). (2) DJ-1 expression was related to tumor recurrence (P < 0.05), but not to sex, age, primary cancer position, T stage, clinical stage, lymph node metastasis and tumor differentiation. Tumor recurrence rate (53.3%) in the patients with higher expression of DJ-1 protein was higher than the rate (26.8%) in the patients with lower expression of DJ-1 protein (χ(2) = 5.164, P < 0.05). (3) With Kaplan-Meier curves and Cox regression analysis, the cumulative 5-year survival rates were correlated with DJ-1 expression levels in laryngeal cancer tissues or cervical lymph node metastasis (all P < 0.05), but not to sex, age, primary cancer position, T stage, clinical stage and tumor differentiation.

CONCLUSIONSThe expression of DJ-1 protein in LSCC is higher than that in control laryngeal mucous tissues. Overexpression of DJ-1 is associated with poor overall survival in LSCC patients.

Adult ; Aged ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Case-Control Studies ; Female ; Humans ; Intracellular Signaling Peptides and Proteins ; metabolism ; Laryngeal Neoplasms ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Oncogene Proteins ; metabolism ; Protein Deglycase DJ-1

OBJECTIVETo investigate the mutation characteristics of DJ1 gene in Chinese patients with autosomal recessive early-onset Parkinsonism (AR-EP).

METHODSMutations of DJ1 gene were screened by polymerase chain reaction combined with DNA direct sequencing in index patients with AR-EP from 11 unrelated families.

RESULTSNo pathogenetic mutations in the DJ1 gene were detected in this group. Six intronic DJ1 polymorphisms (IVS1-15T-->C, IVS4+30T-->G, IVS4+45G-->A, IVS4+46G-->A, IVS5+31G-->A, g.168-185del) were found. Three of them (IVS1-15T-->C, IVS4+45G-->A, IVS4+46G-->A) were not reported previously.

CONCLUSIONDJ1 mutations were rare in Chinese patients with autosomal recessive early-onset Parkinsonism.

Adolescent ; Adult ; Age of Onset ; Base Sequence ; China ; epidemiology ; DNA Mutational Analysis ; methods ; Female ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Mutation ; Oncogene Proteins ; genetics ; Parkinsonian Disorders ; epidemiology ; genetics ; Polymerase Chain Reaction ; Protein Deglycase DJ-1 ; Young Adult

To investigate the effect of Parkinson's disease related protein DJ-1 on the cell proliferation, apoptosis, invasion and migration in human osteosarcoma cells and the underlying molecular mechanisms. 
 Methods: The protein expression levels of DJ-1 were detected in human osteosarcoma cell lines (MG-63, Saos-2, and U2OS) and human osteoblast cell line hFOB1.19 with or without deficiency in phosphatase and tensin homolog deleted from chromosome 10 (PTEN) were detected by Western blot. Osteosarcoma cells were treated with DJ-1 siRNA, and then the protein expression levels of DJ-1 were detected by Western blot. Cell survival rate of osteosarcoma cells was detected by cell counting kit-8 (CCK-8) assay. Cell apoptosis of osteosarcoma cells was measured by annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double staining method. Cell invasive and migration ability of osteosarcoma cells were examined by transwell invasion and migration assay. 
 Results: Compared with that of human osteoblast cell line (hFOB1.19), the protein expression level of DJ-1 was significantly upregulated in human osteosarcoma cell lines (MG-63, Saos-2, and U2OS) (all P<0.05), and U2OS had the highest level of DJ-1 when compared with the other three cell lines (P<0.01). DJ-1 siRNA could significantly down-regulate the DJ-1 protein expression in U2OS cells, and also diminish the cell survival rate. Moreover, DJ-1 down-regulation of DJ-1 could promote cell apoptosis, suppress the ability of cell invasion and migration, and increase the PTEN protein expression level (all P<0.05). In addition, the protein expression level of PTEN was markedly up-regulated in human osteosarcoma cell lines when compared with that in the hFOB1.19 cells (P<0.05). 
 Conclusion: DJ-1 can promote the cell proliferation, inhibit cell apoptosis, and decrease the ability of cell invasion and migration, and the potential underlying mechanisms may be associated with the up-regulation of PTEN protein expression.
Apoptosis ; genetics ; Cell Line, Tumor ; Cell Movement ; genetics ; Cell Proliferation ; genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Invasiveness ; genetics ; PTEN Phosphohydrolase ; genetics ; Parkinson Disease ; physiopathology ; Protein Deglycase DJ-1 ; genetics ; metabolism ; RNA, Small Interfering ; genetics

OBJECTIVE: To investigate the effect of the L10P mutation on the cellular mitochondrial disfunction. METHODS: Spectrophotometer, flow cytometry and electron microscope was utilized to examine cell viability, reactive oxygen species (ROS), mitochondrial transmembrane potential, complex I activity and mitochondrial morphous of the HEK293 monoclone cell lines, in which wild-type and L10P mutant DJ-1 protein are stably expressed. RESULTS: Compared with the cell lines expressing empty vector, we found the ROS levels were elevated, the cell viability, mitochondrial transmembrane potential, complex I activity were reduced in the cells expressing L10P mutant DJ-1 protein (P<0.05). We also found mitochondria in these cells were swelling and some mitochondria were vacuolar degeneration. These phenomena were more obvious when rotenone was used. But in the cells expressing wild-type DJ-1, ROS levels were lower, the cell viability, mitochondrial transmembrane potential, and complex I activity were higher than other cell lines (P<0.05), especially under the induction of rotenone. These results suggested that L10P mutant DJ-1 protein probably lost the ability of anti-oxidative stress and affect the normal function of mitochondria. CONCLUSION The L10P DJ-1 mutation results in a toxic protein, which lacks the protective function of wild-type protein on mitochondria due to the decrease in the ability of anti-oxidative stress.
Cell Survival ; HEK293 Cells ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Membrane Potential, Mitochondrial ; Mitochondria ; pathology ; Mutation ; Oncogene Proteins ; genetics ; Oxidative Stress ; Protein Deglycase DJ-1 ; Reactive Oxygen Species ; metabolism ; Rotenone

BACKGROUND AND OBJECTIVEDJ-1, a suppressor of PTEN, promotes metastasis of different tumors, but its function and mechanisms in glioma metastasis remain unclear. This study aimed to investigate the effect of the DJ-1 protein on the migration and invasion of human glioma cells, and to explore potential mechanisms.

METHODSThe eukaryotic expression vector pEGFP/DJ-1 and small interfering RNA (siRNA) were constructed and transfected into human glioma SWO-38 cells. The expression of DJ-1 and PTEN in SWO-38 cells were detected by Western blot. Cell migration and invasion were detected by transwell assay.

RESULTSAfter transfection of pEGFP/DJ-1, the expression of DJ-1 (1.28 ± 0.15 vs. 0.89 ± 0.04, P < 0.05) and focal adhesion kinase (FAK) phosphorylation (0.76 ± 0.12 vs. 0.51 ± 0.04, P < 0.05) were increased, whereas the expression of PTEN (0.74 ± 0.2 vs. 1.04 ± 0.14, P < 0.05) was suppressed. After transfection of DJ-1 siRNA, both DJ-1 (0.33 ± 0.04 vs. 0.88 ± 0.06, P < 0.05) and p-FAK levels (0.33 ± 0.01 vs. 0.44 ± 0.05, P < 0.05) were decreased, but PTEN expression (1.1 ± 0.06 vs. 0.81 ± 0.12, P < 0.05) was increased. Transwell assay data showed that pEGFP/DJ-1 transfection promoted SWO-38 cell migration (57.2 ± 6.50 vs. 40.4 ± 5.0, P < 0.05) and invasion (54.6 ± 4.9 vs. 27 ± 6.7, P < 0.05), whereas DJ-1 siRNA transfection inhibited SWO-38 cells migration (54.4 ± 6.9 vs. 73.4 ± 7.6, < 0.05) and invasion (44.6 ± 5.8 vs. 69.2 ± 9.2, P < 0.05).

CONCLUSIONOver-expression of DJ-1 promotes SWO-38 cell migration and invasion possibly through the DJ-1 and the PTEN/FAK pathway.

Cell Line, Tumor ; Cell Movement ; Down-Regulation ; Focal Adhesion Protein-Tyrosine Kinases ; metabolism ; Genetic Vectors ; Glioma ; metabolism ; pathology ; Humans ; Neoplasm Invasiveness ; Oncogene Proteins ; genetics ; metabolism ; physiology ; PTEN Phosphohydrolase ; genetics ; metabolism ; Peroxiredoxins ; Phosphorylation ; Plasmids ; Protein Deglycase DJ-1 ; RNA, Small Interfering ; Signal Transduction ; Transfection

OBJECTIVETo study the expression of DJ-1 in human hepatocellular carcinoma and its relationship with tumor invasion and metastasis.

METHODSReverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical methods were used to detect the expression of DJ-1 mRNA and protein in tumor tissue and para-tumor tissue of 46 cases of hepatocellular carcinoma. The relationship between the expression of DJ-1 and clinicopathologic parameters was analyzed.

RESULTSDJ-1 mRNA and protein were expressed in 69.6% and 58.7% of the tumor tissues, which were significantly higher than those in para-tumor tissues (39.1% and 34.8%), chi2 = 8.587, P < 0.05. The increased expression of DJ-1 protein was not correlated with sex of patients, size of tumor, AFP, HBsAg, differentiation level of tumor and hepatocirrhosis (P > 0.05), but with the capsula of tumor, thrombus in the portal vein (P < 0.05).

CONCLUSIONSDJ-1 gene expression may play an important role in the invasion and metastasis of HCC.

Biomarkers, Tumor ; genetics ; metabolism ; Carcinoma, Hepatocellular ; genetics ; metabolism ; pathology ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Intracellular Signaling Peptides and Proteins ; genetics ; metabolism ; Liver Neoplasms ; genetics ; metabolism ; pathology ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Oncogene Proteins ; genetics ; metabolism ; Protein Deglycase DJ-1 ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction