Lysophosphatidylcholie promotes mucus glycoprotein secretion by activating both arachidonic acid cascade and calcium dependent pathways in gallbladder epithelial cells in vitro

Lipoxygenase is an enzyme that metabolizes arachidonic acid down to leukotrienes. Recent studies have shown that the enzyme is implicated in mucous glycoprotein (MGP) secretion stimulated by inflammatory mediators in the airways, suggesting its possible role in secretion of MGP from middle ear epithelial cells. To investigate a correlation between MGP secretion and the arachidonic acid metabolites, we examined the effects of nordihydroguaretic acid (NDGA, both a cyclooxygenase and lipoxygenase inhibitor), low-dose indomethacin (an inhibitor of cyclooxygenase), and A63162 (an inhibitor of lipoxygenase) on MGP secretion in cultured chinchilla middle ear epithelial cells. It was found that lipoxygenase inhibition led to reduction of MGP secretion from cultured chinchilla middle ear epithelial cells, while cyclooxygenase inhibition did not. Both cyclooxygenase and lipoxygenase inhibition resulted in profound blockage of MGP secretion in baseline and platelet activating factor-stimulated MGP secretion. It was concluded, therefore, that MGP secretion was linked to arachidonic acid metabolites, especially lipoxygenase products.

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The In Vitro Effect of Steroid Hormones, Arachidonic Acid, and Kinases Inhibitors on Aquaporin 1, 2, 5, and 7 Gene Expression in the Porcine Uterine Luminal Epithelial Cells during the Estrous Cycle

Cells ◽

10.3390/cells10040832 ◽

2021 ◽

Vol 10 (4) ◽

pp. 832

Author(s):

Damian Tanski ◽

Agnieszka Skowronska ◽

Malgorzata Tanska ◽

Ewa Lepiarczyk ◽

Mariusz T. Skowronski

Keyword(s):

Arachidonic Acid ◽

Epithelial Cells ◽

Steroid Hormones ◽

Estrous Cycle ◽

Kinase Inhibitor ◽

Mapk Signaling ◽

Mapk Kinase ◽

Vitro Effect ◽

Luminal Epithelial Cells

Aquaporins (AQPs) are integral membrane proteins, which play an important role in water homeostasis in the uterus. According to the literature, the expression of aquaporins in reproductive structures depends on the local hormonal milieu. The current study investigated the effect of selected PKA kinase inhibitor H89 and MAPK kinase inhibitor PD98059, on the expression of AQP1, 2, 5, and 7, and steroid hormones (E2), progesterone (P4), and arachidonic acid (AA) in the porcine endometrium on days 18–20 and 2–4 of the estrous cycle (the follicular phase where estrogen and follicle-stimulating hormone (FSH) are secreted increasingly in preparation for estrus and the luteal phase where the ovarian follicles begin the process of luteinization with the formation of the corpus luteum and progesterone secretion, respectively). The luminal epithelial cells were incubated in vitro in the presence of the aforementioned factors. The expression of mRNA was determined by the quantitative real-time PCR technique. In general, in Experiment 1, steroid hormones significantly increased expression of AQP1, 2, and 5 while arachidonic acid increased expression of AQP2 and AQP7. On the other hand, MAPK kinase inhibitor significantly decreased the expression of AQP1 and 5. In Experiment 2, E2, P4, or AA combined with kinase inhibitors differentially affected on AQPs expression. E2 in combination with PKA inhibitor significantly decreased expression of AQP1 but E2 or P4 combined with this inhibitor increased the expression of AQP5 and 7. On the contrary, E2 with PD98059 significantly increased AQP5 and AQP7 expression. Progesterone in combination with MAPK kinase inhibitor significantly downregulated the expression of AQP5 and upregulated AQP7. Arachidonic acid mixed with H89 or PD98059 caused a decrease in the expression of AQP5 and an increase of AQP7. The obtained results indicate that estradiol, progesterone, and arachidonic acid through PKA and MAPK signaling pathways regulate the expression of AQP1 and AQP5 in the porcine luminal epithelial cells in the periovulatory period.

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Meclofenamate sodium is an inhibitor of both the 5-lipoxygenase and cyclooxygenase pathways of the arachidonic acid cascade in vitro

Prostaglandins Leukotrienes and Medicine ◽

10.1016/0262-1746(86)90190-3 ◽

1986 ◽

Vol 23 (2-3) ◽

pp. 229-238 ◽

Cited By ~ 51

Author(s):

Amal M. Boctor ◽

Michele Eickholt ◽

Thomas A. Pugsley

Keyword(s):

Arachidonic Acid ◽

Arachidonic Acid Cascade

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Influence of the arachidonic acid cascade on the in vitro hepatic response to hypoxia

Prostaglandins ◽

10.1016/0090-6980(79)90073-x ◽

1979 ◽

Vol 17 (1) ◽

pp. 39-52 ◽

Cited By ~ 13

Author(s):

John T. Flynn

Keyword(s):

Arachidonic Acid ◽

Arachidonic Acid Cascade

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Interleukin-1β Modulates in Vitro Mucous Glycoprotein Secretion and Proliferation of the Middle Ear Epithelial Cells

Otolaryngology ◽

10.1016/s0194-5998(05)80767-3 ◽

1995 ◽

Vol 113 (2) ◽

pp. P122-P122

Author(s):

Jizhen Lin ◽

Youngki Kim ◽

Chris Lees ◽

Steven K. Juhn

Keyword(s):

Epithelial Cells ◽

Middle Ear ◽

Interleukin 1Β ◽

Glycoprotein Secretion

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α-Conotoxins Enhance both the In Vivo Suppression of Ehrlich carcinoma Growth and In Vitro Reduction in Cell Viability Elicited by Cyclooxygenase and Lipoxygenase Inhibitors

Marine Drugs ◽

10.3390/md18040193 ◽

2020 ◽

Vol 18 (4) ◽

pp. 193

Author(s):

Alexey V. Osipov ◽

Tatiana I. Terpinskaya ◽

Tatsiana Yanchanka ◽

Tatjana Balashevich ◽

Maxim N. Zhmak ◽

...

Keyword(s):

Arachidonic Acid ◽

Antitumor Effect ◽

Nordihydroguaiaretic Acid ◽

Ehrlich Carcinoma ◽

Arachidonic Acid Cascade ◽

Lipoxygenase Inhibitor ◽

Lipoxygenase Inhibitors ◽

Combined Application

Several biochemical mechanisms, including the arachidonic acid cascade and activation of nicotinic acetylcholine receptors (nAChRs), are involved in increased tumor survival. Combined application of inhibitors acting on these two pathways may result in a more pronounced antitumor effect. Here, we show that baicalein (selective 12-lipoxygenase inhibitor), nordihydroguaiaretic acid (non-selective lipoxygenase inhibitor), and indomethacin (non-selective cyclooxygenase inhibitor) are cytotoxic to Ehrlich carcinoma cells in vitro. Marine snail α-conotoxins PnIA, RgIA and ArIB11L16D, blockers of α3β2/α6β2, α9α10 and α7 nAChR subtypes, respectively, as well as α-cobratoxin, a blocker of α7 and muscle subtype nAChRs, exhibit low cytotoxicity, but enhance the antitumor effect of baicalein 1.4-fold after 24 h and that of nordihydroguaiaretic acid 1.8–3.9-fold after 48 h of cell cultivation. α-Conotoxin MII, a blocker of α6-containing and α3β2 nAChR subtypes, increases the cytotoxic effect of indomethacin 1.9-fold after 48 h of cultivation. In vivo, baicalein, α-conotoxins MII and PnIA inhibit Ehrlich carcinoma growth and increase mouse survival; these effects are greatly enhanced by the combined application of α-conotoxin MII with indomethacin or conotoxin PnIA with baicalein. Thus, we show, for the first time, antitumor synergism of α-conotoxins and arachidonic acid cascade inhibitors.

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Benzo[A]pyrene-induced oxidative DNA damage in human mammary epithelial cells: Effects of metabolic intermediates and arachidonic acid cascade inhibitors

Free Radical Biology and Medicine ◽

10.1016/0891-5849(90)90759-c ◽

1990 ◽

Vol 9 ◽

pp. 164 ◽

Cited By ~ 3

Author(s):

Allan N. Tischler ◽

Steven A. Leadon

Keyword(s):

Dna Damage ◽

Arachidonic Acid ◽

Epithelial Cells ◽

Oxidative Dna Damage ◽

Mammary Epithelial Cells ◽

Mammary Epithelial ◽

Arachidonic Acid Cascade ◽

Metabolic Intermediates ◽

Human Mammary Epithelial Cells ◽

Human Mammary Epithelial

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Synergistic Effects of 13-cis Retinoic Acid and Arachidonic Acid Cascade Inhibitors on Growth of Head and Neck Squamous Cell Carcinoma in Vitro

Otolaryngology ◽

10.1016/s0194-5998(98)80004-1 ◽

1998 ◽

Vol 118 (2) ◽

pp. 159-164 ◽

Cited By ~ 10

Author(s):

Aaron Spingarn ◽

Peter G. Sacks ◽

Daniel Kelley ◽

Andrew J. Dannenberg ◽

Stimson P. Schantz

Keyword(s):

Squamous Cell Carcinoma ◽

Arachidonic Acid ◽

Retinoic Acid ◽

Cell Growth ◽

Growth Inhibition ◽

Acid Metabolism ◽

Arachidonic Acid Metabolism ◽

Arachidonic Acid Cascade ◽

Hnscc Cell

Products of arachidonic acid metabolism can influence normal and malignant cell growth. In vivo, inhibitors of arachidonic acid metabolism have been associated with inhibition of tumor growth, including head and neck squamous cell carcinoma (HNSCC). This has not been evaluated extensively in vitro in an HNSCC model. Therefore we investigated the effects of several arachidonic acid cascade inhibitors (AACIs) (indomethacin, curcumin, phenidone, nordihydroguaiaretic acid, 5,8,11,14-eicosatetraynoic acid, and 13- cisretinoic acid) on the growth of two HNSCC cell lines (MDA 886Ln and 1483). We found that AACIs caused dose-dependent growth inhibition of both cell lines. In an effort to inhibit HNSCC cell growth at lower concentrations of these drugs, we evaluated the effects of a variety of AACIs in combination with 13- cis retinoic acid. We observed synergistic growth inhibition when the drugs were used in all combinations, with the exception of indomethacin. These results suggest that AACIs may have some utility in the direct treatment of HNSCC, and a strategy combining 13- cis retinoic acid with other AACIs may prove to be even more effective.

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