Disease relevance of mt-Co1

• Lithium-associated polyuria was also seen in COX1-/- mice and was associated with increased urinary PGE(2) [1].
• The mRNA of COX-1 and -2 was amplified and semi-quantified before and after hypoxia in cells treated or not with indomethacin, a non-selective COX inhibitor [2].
• COX-1 gene disruption also reduced inflammatory edema and joint destruction in female, but not male mice, although females of both COX-/- lines did show some bony destruction [3].
• COX-1 inhibition enhances scratching behaviour in NC/Nga mice with atopic dermatitis [4].
• These results suggest COX-1-coupled skin PGD(2) biosynthesis plays a physiological role in inhibiting regulation of pruritus in NC mice with AD [4].

Psychiatry related information on mt-Co1

• In response to water deprivation, COX2, but not COX1, mRNA levels increase significantly in the renal medulla, specifically in renal medullary interstitial cells (RMICs) [5].
• Surprisingly, on the hot plate (55 degrees C), the COX-1-deficient heterozygous groups showed less nociception, because mean reaction time was longer than that for controls [6].
• The functional significance of cyclooxygenases (COX-1 and -2), the key enzymes that convert arachidonic acid (AA) to prostaglandins (PGs) in brain, is unclear, although they have been implicated in cellular functions and in some neurologic disorders, including stroke, epilepsy, and Alzheimer's disease [7].

High impact information on mt-Co1

• We demonstrate herein that the targeted disruption of COX-2, but not COX-1, in mice produces multiple failures in female reproductive processes that include ovulation, fertilization, implantation, and decidualization [8].
• Cyclooxygenases 1 and 2 (COX-1 and COX-2) are key enzymes in prostaglandin biosynthesis and the target enzymes for the widely used nonsteroidal anti-inflammatory drugs [9].
• NRF-2 also specifically recognizes multiple binding sites in the mouse cytochrome c oxidase subunit Vb (MCO5b) gene [10].
• Therefore, COX-1-selective inhibitors may provide effective treatment to delay preterm labor with fewer adverse effects on fetal or neonatal health than nonselective or COX-2-selective inhibitors [11].
• We utilized wild-type, COX-1(-/-), and COX-2(-/-) mice to demonstrate that COX-2 plays an essential role in both endochondral and intramembranous bone formation during skeletal repair [12].

Chemical compound and disease context of mt-Co1

• CONCLUSIONS: Rofecoxib is protective in acute DSS-induced colitis, probably by reducing neutrophil infiltration, inhibiting up-regulation of IL-1beta and returning to normal COX-1 expression in the inflamed colonic mucosa [13].
• Prostaglandin E2 was increased in polyps compared with normal tissue, and both COX-1 and COX-2 contributed to the PGE2 produced [14].
• In conclusion, these results suggest that TXA(2) is involved in LPS-induced hepatic microcirculatory dysfunction partly through the release of TNF alpha, and that TXA(2) derived from COX-1 and COX-2 could be responsible for the microcirculatory dysfunction during endotoxemia [15].
• Role of thromboxane derived from COX-1 and -2 in hepatic microcirculatory dysfunction during endotoxemia in mice [15].
• In comparison with wild-type and COX-1-/- mice, COX-2-/- mice implanted with Ti had a significantly reduced calvarial bone resorption response, independent of the inflammatory response, and significantly fewer osteoclasts were formed from cultures of their bone marrow cells [16].

Biological context of mt-Co1

• These CTLs recognized a maternally transmitted, H2-M3wt-restricted, minor histocompatibility Ag (MiHA) that is widely distributed among many strains of mice and encoded by the COI mitochondrial gene [17].
• The COI sequence of U.K. H. p. polygyrus is more similar to H. glareoli from voles than to H. p. bakeri, while a single isolate of H. p. polygyrus from Guernsey confirms the extent of genetic variation between H. p. polygyrus populations [18].
• CONCLUSIONS: In mouse, COX-1b encodes a protein with a completely different amino acid sequence than COX-1 or COX-2; therefore it is improbable that COX-1b in this species plays a role in prostaglandin-mediated fever and pain [19].
• Up-regulation of COX1 mRNA in the retina was detected by RT-PCR at 24 hr following the optic nerve injury [20].
• Of these differentially expressed genes, we elected to further examine the increase in COX1 expression, because of data implicating energy utilization in METH neurotoxicity and the known role of COX1 in energy metabolism [21].

Anatomical context of mt-Co1

• Further analyses of rat and mouse COX1 sequences in cells from untampered storage vials of all 11 reported liver progenitor cell lines and strains revealed only mouse sequences [22].
• Similar results were obtained in aortas of female wild-type, COX2 and COX1 knockout mice [23].
• In this study, utilizing RAW 264.7 murine macrophages, we demonstrate that expression of the mitochondrial protein, CCOI, is significantly decreased in the setting of OPN stimulation [24].
• In conclusion, both the expression of COX1 mRNA in retina and the activity of COX in inner plexiform layer and retinal ganglion cell layer were elevated following optic nerve injury without affecting total retinal mitochondrial mass [20].
• On the basis of time course studies, Northern blot analyses, in situ hybridization results, and temperature studies, we now report that increased COX1 expression in the ventral midbrain is linked to METH-induced DA neuronal injury [21].

Associations of mt-Co1 with chemical compounds

• Renal prostaglandin (PG) synthesis is mediated by cyclooxygenase-1 and -2 (COX1 and COX2) [5].
• Treatment of the mice with the selective COX1 inhibitor, piroxicam, attenuated the hypophagic responses to IL-1 and LPS [25].
• In the aorta of the male wild type C57BL/b6 mice (36-40 weeks old), both acetylcholine and the calcium ionophore caused endothelium-dependent increases in force in the presence of L-NAME, and these were inhibited by valeryl salicylate (a selective COX1 inhibitor) and S18886 (a selective antagonist of TP receptors) [23].
• Sequencing the 5' end of the COI gene in LP and C57BL/6 mice showed that the LP allele arose by a T-->C transition in the third codon, which caused substitution of threonine for isoleucine [17].
• However, splenic MØ, isolated from untreated mice and treated in vitro with lipopolysaccharide and interferon-gamma, express COX-1 and COX-2 within 1 day but release only minimal amounts of PGE(2) following elicitation with calcium ionophore A23187 [26].

Regulatory relationships of mt-Co1

• Our results indicate that OPN inhibits CCOI expression as the result of a novel CD44-dependent transcriptional regulatory mechanism of the mitochondrial H strand [24].
• Upstream stimulatory factor 2 stimulates transcription through an initiator element in the mouse cytochrome c oxidase subunit Vb promoter [27].

Other interactions of mt-Co1

• PCR amplification of liver progenitor cell chromosomal (rat and mouse Pigr, rat INS1, mouse INS2) and mitochondrial (rat and mouse COX1) genes revealed only mouse sequences [22].
• The COI mitochondrial gene encodes a minor histocompatibility antigen presented by H2-M3 [17].
• The regions of rRNA, URF1, COI and COIII are generally very conserved regions but areas with some evolutionary activity can be localized [28].
• The amounts of mitochondrial rRNA and the mRNAs for COI and COII varied markedly depending on developmental stage [29].
• The contents of mitochondrial DNA (mtDNA) and the steady-state amounts of 12 and 16 S mitochondrial rRNAs and the mRNAs for cytochrome c oxidase subunits I and II (COI and COII) were determined in dot hybridization experiments with cloned mtDNA fragments as probes during development from the one-cell to the blastocyst stage [29].

Analytical, diagnostic and therapeutic context of mt-Co1

• A semi-quantitative RT-PCR method was then adopted to evaluate the mRNA expression of cytochrome oxidase subunit 1 (COX1) in the retina after surgery [20].
• Cyclooxygenase (COX)-2 plays a harmful role in cerebral ischemic/reperfusion injury, but the role of COX-1 is uncertain [30].
• Indeed, when tested by Western blot analysis with specific COX-1 and COX-2 antibodies, only COX-1 expression could be detected in the bone marrow (BM)-DC [31].
• In contrast, the heptapeptide had no effect on COX-1 mRNA in xenograft tumors or A549 cells [32].
• Although no differences in basal respiratory or lung mechanical parameters were observed, COX-1 Tr mice had increased bronchoalveolar lavage fluid PGE(2) content compared with wild-type littermates (23.0 +/- 3.6 vs 8.4 +/- 1.4 pg/ml; p < 0.05) and exhibited decreased airway responsiveness to inhaled methacholine [33].

References