Human glomerular mesangial cells inactivate leukotriene B4 by reduction into dihydro-leukotriene B4 metabolites

Kaever, Volkhard; Bruuns, J.; Wunder, Jennifer; Damerau, B.; Zimmer, G; Fauler, Joachim; Wessel, Klaus; Floege, Juergen; Topley, Nicholas; Radeke, Heinfried H.; Resch, Klaus

doi:10.1016/0024-3205(90)90463-2

Cited by 18 publications

(3 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In humans, LTB, is metabolized by two different pathways, one of which is w-oxidation in PMN [2][3][4][5][6], the other being the 10, 1 I-reductase pathway in various human cells such as lung macrophage [26], glomerular mesangial cells [27] and keratinocytes [28], and lung tissue [29]. However, little information is available on the metabolism of LTB, in human liver.…”

Section: Northern Blot Analysismentioning

confidence: 99%

Cloning and expression of a novel form of leukotriene B₄ ω‐hydroxylase from human liver

et al. 1994

View full text Add to dashboard Cite

We have isolated and sequenced a cDNA for human liver LTB, w-hydroxylase. The cDNA encoded a protein of 520 amino acids with a molecular weight of 59,853 Da. The cDNA-deduced amino acid sequence showed 87.3% homology to that of human polymorphonuclear leukocytes (PMN) LTB, w-hydroxylase (CYP4F3). Northern blot analysis revealed that the mRNA hybridized to the specific cDNA fragment is expressed in human liver, but not in human PMN. The microsomes from yeast cells transfected with the cDNA catalyzed the o-hydroxylation of LTB4 with a K,,, of 44.8 pM. These results clearly show that a new form of the CYP4F LTB, w-hydroxylase exists in human liver.

show abstract

Section: Northern Blot Analysismentioning

confidence: 99%

Cloning and expression of a novel form of leukotriene B₄ ω‐hydroxylase from human liver

et al. 1994

View full text Add to dashboard Cite

show abstract

“…Recently, 10,11-dihydro derivatives of leukotriene B 4 (LTB 4 ) ( 1 ) have been isolated, , and pathway(s) leading to them and the specific enzymes involved in the route have been investigated . On the basis of the biological activities, 2c, these metabolites are now recognized as initial products of a second metabolic pathway of 1 in addition to the ω-oxidation pathway . The metabolites involve 10,11-dihydro-LTB 4 ( 2 ), , 10,11-dihydro-12- epi -LTB 4 (structure not shown), 2b,c,3d 10,11,14,15-tetrahydro-LTB 4 ( 4 ), 10,11-dihydro-12-oxo-LTB 4 ( 5 ), 2a,b etc.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 10,11-Dihydroleukotriene B₄ Metabolites via a Nickel-Catalyzed Coupling Reaction of cis-Bromides and trans-Alkenyl Borates

Nakayama

Kobayashi

2000

J. Org. Chem.

View full text Add to dashboard Cite

Synthesis of 10,11-dihydro-, 10,11,14,15-tetrahydro-, and 10, 11-dihydro-12-oxoleukotriene B(4) compounds (2, 4, 5) was accomplished stereoselectively by using the nickel-catalyzed coupling reaction illustrated in Scheme 1. The C(1)-C(7) fragments, TBS ether 10a for 2 and 4 and ethyoxyethyl (EE) ether 10b for 5, were prepared in enantiomerically pure forms (>99% ee) by a modified literature procedure (ref 11a). On the other hand, boronate esters 11a and 11b, which correspond to the C(8)-C(20) parts of 2 and 4, respectively, were synthesized from (R)-epichlorohydrin (18) of 99% ee. Briefly, 18 was converted into acetylenes 24 and 32 through epoxide ring-opening with LiC triple bond CC(5)H(11)/BF(3).OEt(2) or C(7)H(15)MgBr/CuCN. Hydroboration of these acetylenes with (+)-(Ipc)(2)BH followed by reaction with MeCHO afforded the corresponding diethyl boronates, which upon ligand exchange with Me(2)C(CH(2)OH)(2) furnished boronate esters 11a and 11b in 75% and 77% yields, respectively. In a similar manner, racemic boronate ester rac-11a, an intermediate for synthesis of 5, was prepared from racemic epichlorohydrin. For synthesis of 2, borate 25 was generated from 11a (1.5 equiv) and MeLi (1.6 equiv). Without isolation, 25 was submitted to reaction with 10a (1 equiv) in the presence of a Ni(0) species at room temperature overnight to afford 26, which upon treatment with TBAF furnished 2 in 64% yield from 10a. Similarly, 11b and 10a furnished 4 in good yield. To synthesize 5, rac-11a and EE ether 10b were joined by the coupling reaction to produce 39, which was transformed into 40 by desilylation with TBAF. After hydrolysis of 40, oxidation with PDC followed by deprotection of the EE group furnished 5 in 36% yield from 40. In addition, 2 was converted into amide 3 in 92% yield.

show abstract

“…The 10,11-dihydro-LTB 4 metabolite ( 4 ) was formed initially and the 12- epi isomer ( 5 ) was only detected following longer incubation times mesangial cells, and human lung . In another study, both epimers of 10,11-dihydro-LTB 4 were detected following a 24-h incubation of LTB 4 with keratinocytes …”

mentioning

confidence: 99%

Synthesis of 10,11-Dihydro-12-oxo-LTB₄, a Key Biochemical Intermediate

et al. 1997

View full text Add to dashboard Cite

show abstract

Human glomerular mesangial cells inactivate leukotriene B4 by reduction into dihydro-leukotriene B4 metabolites

Cited by 18 publications

References 14 publications

Cloning and expression of a novel form of leukotriene B₄ ω‐hydroxylase from human liver

Cloning and expression of a novel form of leukotriene B₄ ω‐hydroxylase from human liver

Synthesis of 10,11-Dihydroleukotriene B₄ Metabolites via a Nickel-Catalyzed Coupling Reaction of cis-Bromides and trans-Alkenyl Borates

Synthesis of 10,11-Dihydro-12-oxo-LTB₄, a Key Biochemical Intermediate

Contact Info

Product

Resources

About

Human glomerular mesangial cells inactivate leukotriene B4 by reduction into dihydro-leukotriene B4 metabolites

Cited by 18 publications

References 14 publications

Cloning and expression of a novel form of leukotriene B4 ω‐hydroxylase from human liver

Cloning and expression of a novel form of leukotriene B4 ω‐hydroxylase from human liver

Synthesis of 10,11-Dihydroleukotriene B4 Metabolites via a Nickel-Catalyzed Coupling Reaction of cis-Bromides and trans-Alkenyl Borates

Synthesis of 10,11-Dihydro-12-oxo-LTB4, a Key Biochemical Intermediate

Contact Info

Product

Resources

About

Cloning and expression of a novel form of leukotriene B₄ ω‐hydroxylase from human liver

Cloning and expression of a novel form of leukotriene B₄ ω‐hydroxylase from human liver

Synthesis of 10,11-Dihydroleukotriene B₄ Metabolites via a Nickel-Catalyzed Coupling Reaction of cis-Bromides and trans-Alkenyl Borates

Synthesis of 10,11-Dihydro-12-oxo-LTB₄, a Key Biochemical Intermediate