Distribution Of Cyclooxygenase Research Articles

Distribution of cyclooxygenase (COX) isoforms in the developing ovine kidney

COX is a rate limiting enzyme in the generation of prostaglandins. COX‐1, the predominant isoform, regulates physiological processes, whereas COX‐2 is typically low and upregulated during inflammation. In the adult kidney, both isoforms are present and localized to various structures implicating their roles in regulating renal haemodynamics and function. When administered during pregnancy or after birth, however, COX inhibitors can decrease renal perfusion and ultrafiltration potentially leading to acute kidney injury in the newborn period. To date, which COX isoform plays a more important role during kidney development is not known. In this study, we assessed the intrarenal distribution of COX‐1 and COX‐2 mRNA and protein expression in the developing ovine kidney, by examining cortical and medullary kidney tissue from lambs aged one day, one‐, three‐, six‐, and twelve weeks (N=3 for each age group). In all age groups, both isoforms were expressed at the level of mRNA and protein. Abundance of COX‐1 mRNA varied between cortex and medulla with an increased expression in the medulla at six and twelve weeks. COX‐2 mRNA was increased in the cortex at day one and week one and in the medulla at three and twelve weeks. Both COX‐1 and COX‐2 protein were greater in medulla than cortex and showed increased expression with postnatal age. These data support a role for both COX isoforms in the developing kidney.

Distribution of cyclooxygenases 1 and 2 in the uterus and breast of cynomolgus monkeys-effects of hormone treatment

The aim of this study was to compare the distribution and immunoreactivity of cyclooxygenase (COX) 1 and COX-2 in normal uterus and breast after long-term hormone therapy in postmenopausal monkeys. Female adult cynomolgus macaques were bilaterally ovariectomized 3 months before the initiation of hormone treatment. The animals were either treated (experiment 1) with conjugated equine estrogens (CEE), medroxyprogesterone acetate (MPA), CEE + MPA, or tamoxifen or designated as controls (C). In experiment 2, the animals were either treated with CEE, CEE + MPA, or tibolone or designated as C. Breast tissue and uteri were collected, fixed, and paraffin embedded. Immunohistochemistry assays for COX-1 and COX-2 were performed. COX-1 immunostaining was decreased by tamoxifen and CEE treatment in the endometrial stroma and by CEE + MPA in the myometrium. COX-1 immunostaining of the breast epithelia was down-regulated by CEE + MPA, whereas other cell types in the breast seem to be less affected by hormone treatment.COX-2 immunoreactivity in the endometrial stroma was increased by CEE + MPA. In the glandular epithelium, CEE + MPA and tibolone treatment increased COX-2 immunostaining compared with CEE treatment only and no treatment at all (C). No effect from hormone treatment on COX-2 immunostaining was found in the myometrium. COX-2 immunostaining in the glandular epithelium of the breast was, in experiment 2, increased after CEE treatment compared with no treatment (C). No other effects by hormone therapy on COX-2 expression were found in the breast. Our results show that COX-1 and COX-2 are differently distributed and regulated by hormones in the normal uterus and breast of ovariectomized macaques. COX-1 is prevailing in the uterus, whereas COX-2 is dominant in the mammary gland.

Cyclo-Oxygenase Distribution in Human Placenta and Decidua Does Not Change with Labour after Term or Preterm Delivery

Our objective was to determine, in an immunohistochemical study, the distribution of cyclo-oxygenase in placental and decidual tissues before and after labour at varying gestations. Subjects were pregnant women undergoing singleton delivery after idiopathic preterm labour at less than 34 weeks' gestation (n = 13); spontaneous term labour at 37-42 weeks' gestation (n = 11); preterm caesarean section at less than 34 weeks' gestation for pre-eclampsia or intrauterine growth retardation (n = 8); elective term caesarean section at 37-42 weeks' gestation for cephalopelvic disproportion (n = 7). Within the placental basal plate cyclo-oxygenase was localised in decidual stromal cells, extravillous trophoblast, and the apical border of villous syncytiotrophoblast, both before and after labour, regardless of gestational age. Within the placental membranes, decidual stromal cells showed intense cytoplasmic cyclo-oxygenase labelling and the chorion laeve strong membrane-associated cyclo-oxygenase reactivity before and after labour, regardless of gestational age. The amnion showed a heterogeneous staining pattern. After labour at term there was either positive cytoplasmic (5/10) or apical staining (5/10). Cyclo-oxygenase was demonstrated in an apical distribution in only 50% of the other subject groups. Cyclo-oxygenase is present in both decidua and placental tissues prior to the onset of labour at term. Demonstration of decidual and trophoblastic cyclo-oxygenase in both preterm and term subjects suggests that differential availability of cyclo-oxygenase is unlikely to be important in preterm delivery. Research into the withdrawal of inhibition or increased substrate availability is most likely to shed light on the signal pathways involved in the onset of labour, regardless of gestation.

Light and electron microscope immunocytochemical localization of 5- and 12-lipoxygenases and cyclooxygenase enzymes in human granulosa cells from preovulatory follicles

Cellular and subcellular distribution of 5- and 12-lipoxygenases and cyclooxygenase enzymes were investigated in human granulosa cells from preovulatory follicles using light and electron microscope immunocytochemistry. The results demonstrated that all three enzymes are present in granulosa cells but not in minor contaminating red blood cells. While the distribution of cyclooxygenase and 12-lipoxygenase was relatively uniform among the granulosa cells, 5-lipoxygenase was not uniformly distributed among these cells. All three enzymes are present in microvillus plasma membranes, rough endoplasmic reticulum, cytoplasm, nuclear membranes and chromatin. In summary, 5- and 12-lipoxygenases and cyclooxygenase enzymes, which catalyze the transformation of arachidonic acid into different eicosanoids, are present in several subcellular organelles including nuclei of granulosa cells from preovulatory follicles.

Eicosanoid Production in Isolated Perfused Lungs Stimulated by Calcium lonophore A23187

The patterns of lung eicosanoid production were investigated in five different species by stimulating isolated lungs with calcium ionophore A23187 (10(-5) M). The species studied were the rat, ferret, hamster, guinea pig, and rabbit. The eicosanoids measured included the cyclooxygenase metabolites 6-keto-PGF1 alpha, TxB2, and PGE2 and the lipoxygenase metabolites LTC4, LTD4, and LTB4. Since these metabolites are either retained in the lungs or released into the perfusate, eicosanoids were measured in lung tissue and in the perfusate. In all animal species, calcium ionophore stimulated the production of all the eicosanoid metabolites measured, although in different relative proportions and quantities. The sulfidopeptide LTC4 was predominantly retained in the lung tissue while other eicosanoids were distributed more evenly between tissue and perfusate, with tissue levels generally being higher. The ferret lung produced large quantities of eicosanoids, more than 90% being lipoxygenase products. In contrast, the guinea pig lung produced predominantly cyclooxygenase products, especially TxB2. The rat, hamster, and rabbit lungs showed a more even distribution of cyclooxygenase and lipoxygenase products. Species differences in the ability to produce lipid mediators in the lung may be important in determining the vasoconstrictive, bronchoconstrictive, or inflammatory response to physiologic stimuli.