Arachidonate 5-lipoxygenase of porcine pancreas: its localization in acinar cells

Natsui, Kiyoshi; Ueda, Natsuo; Yamamoto, Shozo; Komatsú, Noriyuki

doi:10.1016/0005-2760(91)90100-v

Cited by 11 publications

(6 citation statements)

References 22 publications

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“…Immunohistochemistry studies have only shown the 5-LOX expression in porcine pancreatic acinar cells but not in porcine Langerhans islets or ductal cells. 25 Staining was localized along the nuclear membranes of the acinar cells, demonstrated by immunoelectron microscopy. 25 5-LOX expression and distribution was also investigated in rat pancreas, but no evidence of 5-LOX antigen or enzymatic activity was found in exocrine pancreas, purified ␤-cells, or other islet cells.…”

Section: Discussionmentioning

confidence: 99%

“…25 Staining was localized along the nuclear membranes of the acinar cells, demonstrated by immunoelectron microscopy. 25 5-LOX expression and distribution was also investigated in rat pancreas, but no evidence of 5-LOX antigen or enzymatic activity was found in exocrine pancreas, purified ␤-cells, or other islet cells. 39 In contrast, 12-LOX is expressed in islet ␤-cells.…”

Section: Discussionmentioning

confidence: 99%

“…24 Immunohistochemistry has revealed that 5-LOX is expressed in porcine pancreatic acinar cells but not in porcine Langerhans islets or ductal cells. 25 Although weak 5-LOX immunoreactivity has been demonstrated in whole human pancreas extracts, to our knowledge the expression of 5-LOX in human pancreatic ductal cells and ductal adenocarcinoma cells has never been reported. 26 In the present study, the expression of 5-LOX in normal pancreatic ductal cells from a human multiorgan donor and cancer cells was investigated by both nested reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting.…”

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confidence: 81%

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5-Lipoxygenase and Leukotriene B4 Receptor Are Expressed in Human Pancreatic Cancers But Not in Pancreatic Ducts in Normal Tissue

Hennig

Ding

Tong

et al. 2002

The American Journal of Pathology

172

125

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The 5-lipoxygenase (5-LOX) pathway is critical for pancreatic cancer cell growth and escape from apoptosis. Inhibition of 5-LOX blocks proliferation and induces apoptosis in human pancreatic cancer cells. However, the expression of 5-LOX and its downstream signaling pathway have not been investigated in human pancreatic adenocarcinoma. Reverse transcriptase-polymerase chain reaction revealed expression of 5-LOX mRNA in all pancreatic cancer cell lines tested including, PANC-1, AsPC-1, and MiaPaCa2 cells, but not in normal pancreatic ductal cells. The expression of 5-LOX protein in pancreatic cancer cell lines was demonstrated by Western blotting. Finally, 5-LOX up-regulation in human pancreatic cancer tissues was verified by intense positive staining in cancer cells by immunohistochemistry. Staining for the 5-LOX protein was particularly evident in the ductal components of the more differentiated tumors but not in ductal cells in normal pancreatic tissues from cadaver donors. Immunohistochemistry also revealed strong staining of cancer tissues with an antibody to the receptor of the downstream 5-LOX metabolite, leukotriene B(4). The current study demonstrated marked expression of 5-LOX and the leukotriene B(4) receptor in human pancreatic cancer tissues. These findings provide further evidence of up-regulation of this pathway in pancreatic cancer and that LOX inhibitors are likely to be valuable in the treatment of this dreadful disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 81%

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5-Lipoxygenase and Leukotriene B4 Receptor Are Expressed in Human Pancreatic Cancers But Not in Pancreatic Ducts in Normal Tissue

Hennig

Ding

Tong

et al. 2002

The American Journal of Pathology

172

125

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“…However, attempts to identify the enzyme in other tissues yielded results that support the hypothesis that it is expressed in distinctive extrahematopoietic epithelia. Thus, Natsui et al (3) provided evidence that 5-LO protein is present in the nuclear envelope of porcine pancreatic acinar cells, and the studies of Sjolander et al (4) and Dias et al (5) indicated the formation of 5-hydro(pero)xyeicosatetraenoic acid [5-H(P)ETE] and LTB4 in cultured human Henle intestine 407 cells and human colon CaCo-2 cells, respectively. Expression of the 5-LO pathway in skin epithelium likewise remains debatable.…”

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confidence: 99%

Expression of 5-lipoxygenase in differentiating human skin keratinocytes.

Janssen-Timmen

Vickers

Wittig

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

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We studied the expression of arachidonate 5-lipoxygenase (5-LO) in a cell line of human keratinocytes (HaCaT) and in normal human skin keratinocytes in tissue culture. In undifferentiated keratinocytes 5-LO gene expression was low or undetectable as determined by 5-LO mRNA, protein, cell-free enzyme activity, and leukotriene production in intact cells. However, after shift to culture conditions that promote conversion of prokeratinocytes into a more differentiated phenotype, 5-LO gene expression was markedly induced in HaCaT cells and, to a lesser extent, in normal keratinocytes. These results show that 5-LO gene expression is an intrinsic property of human skin keratinocytes.After the discovery of arachidonate 5-lipoxygenase (5-LO; arachidonate:oxygen 5-oxidoreductase, EC 1.13.11.34) in polymorphonuclear neutrophils the enzyme was identified in other leukocyte lineages (1, 2). Products of the 5-LO pathway, including leukotriene (LT) B4 and the cysteinyl LTs, in addition to their roles as inflammatory agonists, may act as physiological autocrine or paracrine signaling molecules. Until recently 5-LO expression was thought to be restricted to the hematopoietic system. However, attempts to identify the enzyme in other tissues yielded results that support the hypothesis that it is expressed in distinctive extrahematopoietic epithelia. Thus, Natsui et al. (3) Expression of the 5-LO pathway in skin epithelium likewise remains debatable. Several authors using primary skin keratinocytes reported the production of 5-hydroxyeicosatetraenoic acid (5-HETE) and LTB4, but subsequent work challenged some of the earlier interpretations (refs. 6-11; for review, see ref. 12).We have used a nontransformed human keratinocyte cell line, HaCaT, and normal human skin keratinocytes (NHKs) as in vitro models to study expression of the 5-LO pathway in extrahematopoietic epithelia. HaCaT cells are derived from a normal skin biopsy and maintain a substantial differentiation potential in culture (13,14). In this report we show that the 5-LO gene is expressed in both HaCaT cells and NHKs under conditions that favor their differentiation. MATERIALS AND METHODS

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“…Very little is known about leukotriene production in the pancreas. It was previously been shown by others that porcine 34 and human 22 pancreatic acinar cells express 5-LO and can synthesize LTB 4 . In addition, the human pancreas also expresses FLAP, 35 but no information was available about the distribution of 5-LO in the mouse pancreas or the effects of inflammatory agents on pancreatic 5-LO activity.…”

Section: Discussionmentioning

confidence: 93%

Acinar Cell Production of Leukotriene B4 Contributes to Development of Neurogenic Pancreatitis in Mice

Shahid

Vigna

Layne

et al. 2015

Cellular and Molecular Gastroenterology and Hepatology

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Background & AimsIn the pancreas, activation of primary sensory nerves through the transient receptor potential vanilloid-1 (TRPV1) ion channel contributes to the early stages of development of pancreatitis. Little is known about the mechanism by which this occurs. We investigated whether leukotriene B4 (LTB4) is an endogenous agonist of TRPV1 and mediates pancreatitis.MethodsAcute inflammation was induced in the pancreata of Trpv1−/− mice and their wild-type littermates by retrograde infusion of the main pancreatic duct with 2% sodium taurocholate (NaT) or intraperitoneal injections of caerulein. Mice were also given injections of resiniferatoxin (an excitotoxin that desensitizes TRPV1) or MK886 (a drug that inhibits LTB4 biosynthesis). Pancreatic tissues and plasma were collected and analyzed.ResultsRetrograde perfusion of the main pancreatic ducts of wild-type mice with NaT caused severe acute pancreatitis; the severity was reduced by coadministration of resiniferatoxin. Trpv1−/− mice developed a less severe pancreatitis after NaT administration compared with controls. Administration of MK886 before perfusion with NaT also significantly reduced the severity of pancreatitis in wild-type mice. Pancreatic tissues from mice given NaT had a marked increase in the level of 5-lipoxygenase immunoreactivity specifically in acinar cells. Bile acid and caerulein induced secretion of LTB4 by cultured pancreatic acinar cells; MK886 inhibited this process.ConclusionsAdministration of caerulein or intraductal bile acids in mice causes production of LTB4 by pancreatic acinar cells. This activates TRPV1 on primary sensory nerves to induce acute pancreatitis.

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Arachidonate 5-lipoxygenase of porcine pancreas: its localization in acinar cells

Cited by 11 publications

References 22 publications

5-Lipoxygenase and Leukotriene B4 Receptor Are Expressed in Human Pancreatic Cancers But Not in Pancreatic Ducts in Normal Tissue

5-Lipoxygenase and Leukotriene B4 Receptor Are Expressed in Human Pancreatic Cancers But Not in Pancreatic Ducts in Normal Tissue

Expression of 5-lipoxygenase in differentiating human skin keratinocytes.

Acinar Cell Production of Leukotriene B4 Contributes to Development of Neurogenic Pancreatitis in Mice

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