Disease relevance of SEMA3A

• Exogenous SEMA3A expressed in 293 or U87MG cells has no collapsing or chemorepulsive activities on glioma cells as determined by F-actin staining and collagen coculture assays [1].
• Loss of inhibitory semaphorin 3A (SEMA3A) autocrine loops in bone marrow endothelial cells of patients with multiple myeloma [2].
• Strong expression of SEMA was found in 48% of benign, 33% of borderline tumors, and 13% of carcinomas (P < .05) [3].
• A high VEGF/SEMA ratio has adverse prognostic significance in patients with ovarian carcinoma [3].
• Isolation of the human semaphorin III/F gene (SEMA3F) at chromosome 3p21, a region deleted in lung cancer [4].

Psychiatry related information on SEMA3A

• OBJECTIVE: To identify and compare the patterns of cerebral atrophy associated with two clinical variants of frontotemporal lobar degeneration (FTLD): frontotemporal dementia (FTD) and semantic dementia (SemD) [5].
• The authors suggest that pathology in the areas of atrophy associated with both FTD and SemD may underlie some the behavioral symptoms seen in the two disorders [5].
• METHODS: The authors asked patients with progressive nonfluent aphasia (PNFA), patients with semantic dementia (SemD), and nonaphasic patients with a disorder of social comportment and executive functioning (SOC/EXEC) to narrate the story of a wordless children's picture book [6].

High impact information on SEMA3A

• Both the sema portion and the remainder of the ectodomain of PlexinA1 associate with NP1 in a Sema3A-independent fashion [7].
• Winberg et al. present evidence that the transmembrane protein Off-track (OTK) interacts biochemically and genetically with Plexin A and is important for Sema 1a repulsive signaling [8].
• Sema-deleted PlexinA1 is constitutively active, producing cell contraction, growth cone collapse, and inhibition of neurite outgrowth [7].
• The coagulation factor domains alone are necessary and sufficient for binding of the Sema III immunoglobulin- (Ig-) basic domain and the unrelated ligand, vascular endothelial growth factor (VEGF) [9].
• Enteroaggregative Escherichia coll and outbreaks of gastroenteritis in UK [10].

Chemical compound and disease context of SEMA3A

• The most common pathogens isolated were Escherichia coll, Streptococcus pneumoniae, P. aeruginosa, K. pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and Streptococcus, group B. Overall, approximately 94% of pathogens isolated in pretreatment cultures were susceptible to cefepime and ceftazidime [11].

Biological context of SEMA3A

• Further, all glioma cell lines express SEMA3A and SEMA3C and exhibit SEMA3A binding sites [1].
• In contrast, other human semaphorin gene sequences (human semaphorin III and homologues of murine semaphorins B and C) are not located on chromosome 3 [12].
• In addition, loss of heterozygosity at SEMA gene loci was examined [3].
• Recombinant sema 3C induced MGEC proliferation 18 +/- 2% above control, as assessed by bromodeoxyuridine (BrdU) incorporation, and reduced starvation-induced apoptosis by 46 +/- 3%, as indicated by an in situ marker of activated caspase 3 [13].
• Sema 3A expressed by endothelial cells controls vascular morphogenesis through integrin inhibition [13].

Anatomical context of SEMA3A

• We have employed an expression cloning strategy to search for axon repellents secreted by the notochord, and have identified SEMA3A as a candidate repellent [14].
• In contrast to most previously described semaphorins, sema K1 is only weakly expressed during development but is present at high levels in postnatal and adult tissues, particularly brain and spinal cord [15].
• We report that a factor secreted in the umbilical cord induces the collapse of neurite growth cones in vitro and provide evidence that this factor is Sema 3A [16].
• In summary, our results suggest that the chemorepulsive signals mediated by Sema 3A play an important role in preventing nerve fibers growth in the umbilical cord and in gestational uterine tissues [16].
• It turns out that paracrine secretion of class 3 SEMA (SEMA3) by nonendothelial tissues cooperates with vascular endothelial growth factor in regulating EC precursor migration and assembly during vasculogenesis and funnels navigating blood vessel through tissue boundaries during sprouting angiogenesis [17].

Associations of SEMA3A with chemical compounds

• TSA and SAHA upregulated the expression by HUVEC of semaphorin III, a recently described VEGF competitor, at both mRNA and protein levels [18].
• Indeed, signaling from SEMA-activated plexin receptors negatively regulates cell-ECM adhesive interactions by inhibiting two key integrin activators, such as the small GTPase R-Ras and the focal adhesion protein talin [17].
• We show that three different GSK-3 antagonists (LiCl, SB-216763, and SB-415286) can inhibit the growth cone collapse response induced by Sema 3A [19].
• The sema domain was first defined from sequence by Kolodkin and colleagues in the early 1990s, and constitutes the distinctive structural and functional element of semaphorins, their plexin receptors and the receptor tyrosine kinases MET and RON, three protein families with major roles in development, tissue regeneration and cancer [20].
• Mutation of cysteine 723, one of four conserved cysteine residues in the 33-kDa fragment, revealed its requirement both for the dimerization of SemD and its chemorepulsive activity [21].

Physical interactions of SEMA3A

• The neuropilin (NP)/plexin (Plex) Rc complex binds Sema [22].

Other interactions of SEMA3A

• Neuropilin-1 is a receptor for Sema III [9].
• Here we provide evidence that breast carcinoma cells support an autocrine pathway involving SEMA3A, plexin-A1, and NP1 that impedes their ability to chemotax [23].

Analytical, diagnostic and therapeutic context of SEMA3A

• To determine whether skeletal unloading also induced resistance to GH, we evaluated the response of the femur and humerus of sham and hypophysectomized rats, control and hind limb elevated, to GH (two doses), measuring mRNA levels of IGF-I, BGP, rat bone alkaline phosphatase (RAP), and alpha 1(1)-procollagen (coll) [24].
• Retrograde tracing combined with in situ hybridization also revealed that the staining of semaIII/coll-1 within the entorhinal cortex was present in the stellate neurons that project via the perforant path to the molecular layer of the dentate gyrus [25].
• From the comparison between glass transition (T'g) and collapse (T coll) temperatures, we concluded that the collapse temperature was a more relevant parameter than T'g for freeze-drying cycle development and optimisation [26].
• Furthermore, human cartilage proteoglycans and II coll, assayed by specific radioimmunoassays, are released into the culture medium and constitute the new matrix of the clusters [27].

References