| 1 | Behav Brain Funct 2010 -1 6: 44 |
|---|---|
| PMID | 20626912 |
| Title | 变形之间的联系isms of arachidonate 12-lipoxygenase (ALOX12) and schizophrenia in a Korean population. |
| Abstract | Arachidonic acid (AA), an essential polyunsaturated fatty acid, is one of the major components of neural membranes, which show an altered phospholipid composition inschizophrenia. Arachidonate 12-lipoxygenase (ALOX12), an important enzyme, metabolizes AA to 12-HPETE, which affects catecholamine synthesis. However, research has yet to show the genetic association betweenALOX12andschizophrenia. Therefore, we investigated single nucleotide polymorphisms (SNP) of theALOX12gene inschizophrenia, recruiting patients withschizophrenia(n = 289) and normal controls (n = 306) from a Korean population. We selected three SNPs (rs1126667, rs434473, and rs1042357) of theALOX12gene and genotyped them by direct sequencing. We reviewed theschizophrenicpatients' medical records and assessed them clinically using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), and the Operational Criteria Checklist (OPCRIT). Then we statistically analyzed the genetic associations between the SNPs andschizophrenia, finding a genetic association between both rs1126667 and rs1042357 andschizophrenia, in the recessive model (p = 0.015 and 0.015, respectively). We also found an association between rs434473 and negative symptoms, defined through a factor analysis of the OPCRIT data (p = 0.040). Consequently, we suggest that SNPs of theALOX12gene might be associated withschizophreniaand negative symptoms in this Korean population. These weak positives require additional study. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Behav Brain Funct 2010 -1 6: 44 |
| PMID | 20626912 |
| Title | 变形之间的联系isms of arachidonate 12-lipoxygenase (ALOX12) and schizophrenia in a Korean population. |
| Abstract | Arachidonic acid (AA), an essential polyunsaturated fatty acid, is one of the major components of neural membranes, which show an altered phospholipid composition inschizophrenia. Arachidonate 12-lipoxygenase (ALOX12), an important enzyme, metabolizes AA to 12-HPETE, which affects catecholamine synthesis. However, research has yet to show the genetic association betweenALOX12andschizophrenia. Therefore, we investigated single nucleotide polymorphisms (SNP) of theALOX12gene inschizophrenia, recruiting patients withschizophrenia(n = 289) and normal controls (n = 306) from a Korean population. We selected three SNPs (rs1126667, rs434473, and rs1042357) of theALOX12gene and genotyped them by direct sequencing. We reviewed theschizophrenicpatients' medical records and assessed them clinically using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), and the Operational Criteria Checklist (OPCRIT). Then we statistically analyzed the genetic associations between the SNPs andschizophrenia, finding a genetic association between both rs1126667 and rs1042357 andschizophrenia, in the recessive model (p = 0.015 and 0.015, respectively). We also found an association between rs434473 and negative symptoms, defined through a factor analysis of the OPCRIT data (p = 0.040). Consequently, we suggest that SNPs of theALOX12gene might be associated withschizophreniaand negative symptoms in this Korean population. These weak positives require additional study. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Infect. Immun. 2014 Jul 82: 2670-9 |
| PMID | 24686056 |
| Title | ALOX12 in human toxoplasmosis. |
| Abstract | ALOX12is a gene encoding arachidonate 12-lipoxygenase (12-LOX), a member of a nonheme lipoxygenase family of dioxygenases.ALOX12催化花生四烯酸的加入氧气acid, producing 12-hydroperoxyeicosatetraenoic acid (12-HPETE), which can be reduced to the eicosanoid 12-HETE (12-hydroxyeicosatetraenoic acid). 12-HETE acts in diverse cellular processes, including catecholamine synthesis, vasoconstriction, neuronal function, and inflammation. Consistent with effects on these fundamental mechanisms, allelic variants ofALOX12are associated with diseases includingschizophrenia, atherosclerosis, and cancers, but the mechanisms have not been defined. Toxoplasma gondii is an apicomplexan parasite that causes morbidity and mortality and stimulates an innate and adaptive immune inflammatory reaction. Recently, it has been shown that a gene region known as Toxo1 is critical for susceptibility or resistance to T. gondii infection in rats. An orthologous gene region withALOX12centromeric is also present in humans. Here we report that the humanALOX12gene has susceptibility alleles for human congenital toxoplasmosis (rs6502997 [P, <0.000309], rs312462 [P, <0.028499], rs6502998 [P, <0.029794], and rs434473 [P, <0.038516]). A human monocytic cell line was genetically engineered using lentivirus RNA interference to knock downALOX12. InALOX12knockdown cells,ALOX12RNA expression decreased and levels of theALOX12substrate, arachidonic acid, increased.ALOX12knockdown attenuated the progression of T. gondii infection and resulted in greater parasite burdens but decreased consequent late cell death of the human monocytic cell line. These findings suggest thatALOX12influences host responses to T. gondii infection in human cells.ALOX12has been shown in other studies to be important in numerous diseases. Here we demonstrate the critical roleALOX12plays in T. gondii infection in humans. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Arch. Toxicol. 2014 Mar 88: 691-9 |
| PMID | 24352538 |
| Title | Inhibition of tumour spheroid-induced prometastatic intravasation gates in the lymph endothelial cell barrier by carbamazepine: drug testing in a 3D model. |
| Abstract | Metastatic breast cancer is linked to an undesired prognosis. One early and crucial metastatic step is the interaction of cancer emboli with adjacent stroma or endothelial cells, and understanding the mechanisms of this interaction provides the basis to define new targets as well as drugs for therapy and disease management. A three-dimensional (3D) co-culture model allowing the examination of lymphogenic dissemination of breast cancer cells was recently developed which facilitates not only the study of metastatic processes but also the testing of therapeutic concepts. This 3D setting consists of MCF-7 breast cancer cell spheroids (representing a ductal and hormone-dependent subtype) and of hTERT-immortalised lymph endothelial cell (LEC; derived from foreskin) monolayers. Tumour spheroids repel the continuous LEC layer, thereby generating "circular chemorepellent-induced defects" (CCIDs) that are reminiscent to the entry gates through which tumour emboli intravasate lymphatics. We found that the ion channel blocker carbamazepine (which is clinically used to treat epilepsy,schizophreniaand other neurological disorders) inhibited CCID formation significantly. This effect correlated with the inhibition of the activities of NF-?B, which contributes to cell motility, and with the inactivation of the mobility proteins MLC2, MYPT1 and FAK which are necessary for LEC migration. NF-?B activity and cell movement are prerequisites of CCID formation. On the other hand, the expression of the motility protein paxillin and of the NF-?B-dependent adhesion mediator ICAM-1 was unchanged. Also the activity ofALOX12was unaffected.ALOX12is the main enzyme synthesising 12(S)-HETE, which then triggers CCID formation. The relevance of the inhibition of CYP1A1, which is also involved in the generation of mid-chain HETEs such as 12(S)-HETE, by carbamazepine remains to be established, because the constitutive level of 12(S)-HETE did not change upon carbamazepine treatment. Nevertheless, the effect of carbamazepine on the inhibition of CCID formation as an early step of breast cancer metastasis was significant and substantial (~30 %) and achieved at concentrations that are found in the plasma of carbamazepine-treated adults (40-60 ?M). The fact that carbamazepine is a drug approved by the US Food and Drug Administration facilitates a "from-bench-to-bedside" perspective. Therefore, the here presented data should undergo scrutiny in vivo. |
| SCZ Keywords | schizophrenia, schizophrenic |