Expression of Arachidonate 12-Lipoxygenase in Rat Tissues: A Possible Role in Glucagon Secretion

Kawajiri, Hiroo; Zhuang, Daming; Qiao, Na; Yoshimoto, Tanihiro; Yamamoto, Miyuki; Iseki, Shoichi; Hamaguchi, Kazuyuki

doi:10.1177/002215540004801011

Cited by 19 publications

(17 citation statements)

References 34 publications

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“…Preliminary experiments checked the cross-reactivity of the used antibodies against respective LOX antigens with lung (ALOX5 and -12) and spleen (ALOX12) positive controls. As was consistent with the previously reported results (Maruyama et al 1989, Covin et al 1998, Kawajiri et al 2000, alveolar epithelial cells in the lung and white pulp in the spleen of adult rats showed positive immunoreaction for respective antigen (data not shown).…”

Section: Distribution Of Immunoreactive Lox Isoforms In the Preovulatsupporting

confidence: 93%

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Inhibition of ovulation by a lipoxygenase inhibitor involves reduced cyclooxygenase-2 expression and prostaglandin E2 production in gonadotropin-primed immature rats

Kurusu¹,

Jinno²,

Ehara³

et al. 2009

Reproduction

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Potential roles of cyclooxygenase (COX) pathway of arachidonic acid (AA) metabolism are established in a murine model of induced ovulation. Pharmacological inhibition of an alternative lipoxygenase (LOX) pathway has been shown to cause defective ovulation, but the mechanism is still undefined. This study investigated the effects of two LOX inhibitors and their time dependency on ovulation and COX activity in gonadotropins (eCG and human chorionic gonadotropin (hCG))-primed immature rats. Intra-ovarian bursal treatment with a general LOX inhibitor nordihydroguaiaretic acid (NDGA) at 0 h post-hCG (hCG0h) dose dependently inhibited ovulation rate. The drug was still but less effective when treated at hCG6h. A more specific inhibitor, 3,4-dihydroxyphenyl ethanol (DPE) was also inhibitory when treated at hCG0h but not at hCG6h. Interestingly, treatment with DPE at hCG0h resulted in attenuated expression of immunoreactive PTGS2 in granulosa layers and concomitant decrease in ovarian prostaglandin E 2 (PGE 2 ) content at hCG8h. NDGA treatment reduced immunoreactive PTGS2. Ovulatory impairment by both inhibitors was prevented by systemic administration of PGE 2 at hCG6h. Immunohistochemistry revealed the expression of ALOX5 and ALOX12 in both thecal and granulosa layers of preovulatory follicles and, notably, the augmented immunoreactivities during 8 h after hCG treatment. Our results indicate the probable presence of multiple LOX isoforms and that specific inhibition of LOX at an early stage of hCG-signaling led to reduced PTGS2 activity and thus defective ovulation. They reveal a probable relationship between two pathways of AA metabolism and account at least partly for the mechanism by which the LOX inhibitor causes impaired ovulation.

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Section: Distribution Of Immunoreactive Lox Isoforms In the Preovulatsupporting

confidence: 93%

“…This experiment was also carried out for three different samples at each time point. Sections of lung and spleen of adult rats served as positive controls for ALOX5 (lung) and ALOX12 (lung and spleen) immunohistochemistry (Maruyama et al 1989, Covin et al 1998, Kawajiri et al 2000.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Inhibition of ovulation by a lipoxygenase inhibitor involves reduced cyclooxygenase-2 expression and prostaglandin E2 production in gonadotropin-primed immature rats

Kurusu¹,

Jinno²,

Ehara³

et al. 2009

Reproduction

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“…Leucocyte type 12LO has been demonstrated to be expressed in mouse and rat islets [8,9]. In addition, we have preliminary data indicating that insulin-releasing beta cells Fig.…”

Section: Discussionmentioning

confidence: 53%

“…They are platelet, leucocyte and epidermal 12LO with distinctive tissue distribution, substrate and product specificity. In contrast to platelet 12LO, leucocyte 12LO is widely distributed, including in the endocrine pancreas [8,9].…”

Section: Introductionmentioning

confidence: 99%

Activation of 12-lipoxygenase in proinflammatory cytokine-mediated beta cell toxicity

et al. 2005

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Aims/hypothesis: Beta cell inflammation and cytokine-induced toxicity are central to autoimmune diabetes development. Lipid mediators generated upon lipoxygenase (LO) activation can participate in inflammatory pathways. 12LO-deficient mice are resistant to streptozotocin-induced diabetes. This study sought to characterise the cellular processes involving 12LO-activation lipid inflammatory mediator production in cytokine-treated pancreatic beta cells. Methods: Islets and beta cell lines were treated with a combination of IL-1β, IFN-γ and TNF-α, or the 12LO product 12(S)-hydroxyeicosatetraenoic acid (HETE). Insulin secretion was measured using an enzyme immunoassay, and cell viability was evaluated using an in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assay. 12LO activity was evaluated and 12LO protein levels were determined using immunoblotting with a selective leucocyte type 12LO antibody. Cellular localisation of 12LO was evaluated using immunocytochemistry. Results: Basal expression of leucocyte type 12LO protein was found in human and mouse islets and in several rodent beta cell lines. In mouse β-TC3 cells, and in human islets, cytokines induced release of 12-HETE within 30 min. Cytokine addition also induced a rapid translocation of 12LO protein from the cytosol to the nucleus of β-TC3 cells as shown by subcellular fractionation and immunostaining. Cytokine-induced cell death and inhibition of insulin secretion were partially reversed by baicalein, a 12LO inhibitor. 12(S)-HETE inhibited β-TC3 cell insulin release in a time-and concentration-dependent manner. Incubating β-TC3 cells with 100 nmol/l of 12(S)-HETE resulted in a 57% reduction in basal insulin release (6 h), and a 17% increase in cell death (18 h) as compared with untreated cells. 12(S)-HETE activated the stress-activated protein kinase c-Jun N-terminal kinase and p38 within 15 min, as judged by increased kinase protein phosphorylation. Conclusions/interpretation: The data suggest that inflammatory cytokines rapidly activate 12LO and show for the first time that cytokines induce 12LO translocation. The effects of 12-HETE on insulin secretion, cytotoxicity and kinase activation were similar to the effects seen with cytokines. The results provide mechanistic information of cytokine-induced toxic effects on pancreatic beta cells and support the hypothesis that blocking 12LO activation could provide a new therapeutic way to protect pancreatic beta cells from autoimmune injury.

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“…Transgenic rats harboring the mouse Ren-2 gene, referred to as TGR(mREN2) 27,8 exhibit salt-sensitive hypertension, low active plasma renin levels, suppressed kidney renin, high plasma inactive (pro) renin, and high extrarenal transgene expression, most prominently in the adrenal cortex. Notably, adrenal steroidogenesis is markedly enhanced in these rats, suggesting a possible role for the adrenal RAS in adrenocortical steroidogenesis.…”

Section: Morizane Et Al Aberrant Aldosterone Production In Dahl-s Ratmentioning

confidence: 99%

Biphasic Time Course of the Changes in Aldosterone Biosynthesis Under High-Salt Conditions in Dahl Salt-Sensitive Rats

Morizane

Mitani

Ozawa

et al. 2012

ATVB

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Objective-The comorbidity of excess salt and elevated plasma aldosterone has deleterious effects in cardiovascular disease. We evaluated the mechanisms behind the paradoxical increase in aldosterone biosynthesis in relation to dietary intake of salt. Methods and Results-Dahl salt-sensitive (Dahl-S) and salt-resistant (Dahl-R) rats were fed a high-salt diet, and plasma and tissue levels of aldosterone in the adrenal gland and heart were quantified by liquid chromatography-electrospray ionization-tandem mass spectrometry. In Dahl-S rats, we found that the delayed and paradoxical increase in aldosterone biosynthesis after the initial and appropriate response to high salt. The late rise in aldosterone biosynthesis was accompanied by upregulation of CYP11B2 expression in the zona glomerulosa and increased adrenal angiotensin II levels and renin-angiotensin system components. It preceded the appearance of left ventricular systolic dysfunction and renal insufficiency. Blockade of angiotensin AT 1 receptors reversed the paradoxical increase in aldosterone biosynthesis. In contrast, Dahl-R rats maintained the initial suppression of aldosterone biosynthesis. Aldosterone levels in the heart closely paralleled those in the plasma and adrenal gland and disappeared after bilateral adrenalectomy. Conclusion-Chronic salt overload in Dahl-S rats stimulates aberrant aldosterone production via activation of the local renin-angiotensin system in the adrenal gland, thereby creating the comorbidity of excess salt and elevated plasma aldosterone. (Arterioscler Thromb Vasc Biol . 2012;32:1194-1203 .)

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Expression of Arachidonate 12-Lipoxygenase in Rat Tissues: A Possible Role in Glucagon Secretion

Cited by 19 publications

References 34 publications

Inhibition of ovulation by a lipoxygenase inhibitor involves reduced cyclooxygenase-2 expression and prostaglandin E2 production in gonadotropin-primed immature rats

Inhibition of ovulation by a lipoxygenase inhibitor involves reduced cyclooxygenase-2 expression and prostaglandin E2 production in gonadotropin-primed immature rats

Activation of 12-lipoxygenase in proinflammatory cytokine-mediated beta cell toxicity

Biphasic Time Course of the Changes in Aldosterone Biosynthesis Under High-Salt Conditions in Dahl Salt-Sensitive Rats

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