Disease relevance of Park7

• DJ-1 is the third gene that has been linked to Parkinson disease [1].
• Amino acid sequences obtained following Edman degradation of purified SP22 protein and cDNA sequence data both indicated that SP22 was a member of a highly conserved and widely expressed gene family found in organisms as diverse as human and Escherichia coli [2].
• The association of ornidazole- and alpha-chlorohydrin-induced infertility with the presence of CAP1 in epididymal fluid, probably originating from spermatozoa, suggests a critical role for this protein in fertilization [3].
• Immunoblots indicated that affinity-purified anti-rSP22 immunoglobulin (Ig) and ascites Ig recognized denatured and native SP22, respectively [4].
• In the present study we sought to establish whether equimolar exposure to bromochloroacetic acid (BCA), a prevalent by-product in finished drinking water, is also capable of disrupting these endpoints, and if so to determine whether the novel biomarker of fertility (SP22) would be correlated with subfertility induced by testicular toxicity [5].

High impact information on Park7

• Our data indicate that DJ-1 protects dopaminergic neurons from oxidative stress through up-regulation of glutathione synthesis and from the toxic consequences of mutant humanalpha-synuclein through increased expression of heat shock protein 70 [1].
• We have found that DJ-1 improves survival by increasing cellular glutathione levels through an increase in the rate-limiting enzyme glutamate cysteine ligase [1].
• In the rat dopaminergic cell line, N27, and in primary dopamine neurons, overexpression of wild type DJ-1 protected cells from death induced by hydrogen peroxide and 6-hydroxydopamine [1].
• We conclude that DJ-1 has multiple specific mechanisms for protecting dopamine neurons from cell death [1].
• The aim of this study was to examine whether SP-22 is involved in mitochondrial antioxidant mechanisms and whether its expression is induced by oxidative stresses, particularly those in mitochondria [6].

Chemical compound and disease context of Park7

• Under defined experimental conditions tilorone hydrochloride also prevented pulmonary metastases from a subcutaneous tumour graft of epithelioma SP1 and mammary carcinoma SP22, as measured by an increased survival or treated rats [7].

Biological context of Park7

• Wild type DJ-1 reduced cellular reactive oxygen species and reduced the levels of protein oxidation caused by oxidative stress [1].
• The gene for CAP1 has been isolated from a rat testis cDNA library and its expression investigated in different tissues [8].
• Three nucleotide sequences encoding SP22, a protein originally identified in detergent extracts of cauda epididymal sperm, were isolated from a rat testis cDNA library [2].
• Although no conclusive function has been attributed to any members of the SP22 gene family, the localization of SP22 over a discrete region of the sperm head suggests a pivotal role in sperm-egg interactions [2].
• SP22 has been implicated in apoptosis, androgen receptor function, fertility, and ontogeny of early-onset Parkinson's disease [9].

Anatomical context of Park7

• Moreover, affinity-purified anti-SP22 peptide immunoglobulin localized in a highly specific manner to the anterior-ventral surface of the equatorial segment of the sperm head [2].
• Localization of fertility factor SP22 to specific cell types within the anterior pituitary gland [9].
• We cloned the cDNA for full-length SP22 from AP and posterior lobe (posterior pituitary and intermediate lobe) of the pituitary gland in adult male rats and Golden Syrian hamsters, confirming the presence of SP22 mRNA in the AP and posterior lobe [9].
• CAP1 was present in spermatozoa from the caput epididymidis but not from the rete testis in control animals [3].
• In vitro incubations of tissue from the caput, corpus, and cauda epididymidal regions with [35S]methionine gave no hint that CAP1 was a secretion product of the epididymal epithelium [3].

Associations of Park7 with chemical compounds

• Blocking glutathione synthesis eliminated the beneficial effect of DJ-1 [1].
• Epididymal fluid from rats rendered infertile by oral administration of ornidazole contains a protein CAP1 (contraception-associated protein 1) that is absent from epididymal fluid, but present on epididymal sperm, from fertile vehicle-treated rats [8].
• SP22 did not differ with treatment, indicating that AP SP22 concentration was not regulated by testosterone [9].
• To localize SP22 to specific cells of the AP, mirror-image paraffin sections were labeled against SP22 and either luteinizing hormone (LH)beta, thyroid-stimulating hormone (TSH)beta, prolactin, adrenocorticotropic hormone (ACTH), or growth hormone (GH) using peroxidase-conjugated secondary antibody [9].
• The expression of SP-22 mRNA increased 2.0-3.5-fold with a peak at 3-6 h after exposure to Fe2+/dithiothreitol or a respiratory inhibitor, antimycin A [6].

Other interactions of Park7

• We found a manifold decrease in annexin VII, heat-shock cofactor HOP/p60 and SP-22 and a manifold increase in heparin-binding protein p30 [10].

Analytical, diagnostic and therapeutic context of Park7

• Anti-SP22 peptide antiserum was shown to recognize a family of 22-kDa proteins on western blots of detergent-extracted cauda epididymal sperm protein, suggesting that multiple charge variants of SP22 coexist [2].
• Northern blot hybridisation from different rat tissues indicated that CAP1 is encoded by a 1.6-kilobase RNA transcript and seems to be ubiquitiously expressed in the rat with a high level of expression in the testis [8].
• Molecular cloning and expression of rat contraception associated protein 1 (CAP1), a protein putatively involved in fertilization [8].
• Infrared matrix-assisted laser desorption/ionization mass spectrometry indicated that the molecular mass of CAP1 was 20420+/-120 daltons [3].
• Linear epitope mapping of the 189-amino acid SP22 sequence revealed 3 distinct peptide sequences recognized by anti-rSP22 Ig, and 1 sequence recognized by ascites Ig [4].

References