Masako Morikawa

Regulated expression of acyl-CoA thioesterases in the differentiation of cultured rat brown adipocytes.

Acyl-CoA thioesterases (ACOTs) are enzymes that catalyze the hydrolysis of fatty acyl-CoAs to free fatty acids and CoA-SH. In this study, we show that the expression profile of the ACOT isoforms changes remarkably during the differentiation of cultured rat brown adipocytes. Immunocytochemistry suggested that cytosolic ACOT1 was present in the preadipocytes, while mitochondrial ACOT2 was additionally expressed as the cells differentiated, concurrent with the accumulation of lipid droplets in the cytoplasm. Western blotting confirmed that, in contrast to ACOT1, the ACOT2 expression level was very low in the preadipocytes. However, after differentiation, the ACOT1 level fell to one-half of the baseline level and ACOT2 increased 18-fold. ACOT2 expression in the differentiated adipocytes was further enhanced by treatment with lipids or troglitazone. These changes in the ACOT2 expression level correlated well with changes in the expression of carnitine palmitoyltransferase 2, a mitochondrial β-oxidation enzyme. These results indicate that, in differentiating brown adipocytes, cytosolic ACOT1 becomes downregulated as the cellular use of acyl-CoA increases, while mitochondrial ACOT2 is upregulated as the β-oxidation capacity increases. ACOT isoform expression may be regulated during brown adipocyte differentiation to support the fat storage and combustion characteristics of this cell type.

Effect of mammalian lignans on f MLP‐induced oxidative bursts in human polymorphonuclear leucocytes

Abstract— We examined the effects of mammalian lignans, enterolactone, prestegane B and 2,3‐dibenzylbutane‐1,4‐diol (DBB) on superoxide production and luminol‐dependent chemiluminescence (LCL) response in human polymorphonuclear leucocytes (PMNs). The three lignans had no direct effect on the responses of human PMNs. DBB and prestegane B enhanced the superoxide production and LCL response induced by formylmethionyl‐leucyl‐phenyl‐alanine (f MLP), but enterolactone inhibited f MLP‐induced effects. The effects of DBB were stronger than those of prestegane B and the effects of DBB were inhibited by bromophenacyl bromide, mepacrine, N‐(6‐aminophenyl)‐5‐chloro‐t‐naphthalene sulphonamide and trifluoroperazine, but not by gossypol, nordihydroguaretic acid, indomethacin, staurosporine, 1‐(5‐isoquinolinesulphonyl)‐2‐methylpiperazine dihydrochloride or (R,S)‐2‐methoxy‐3‐(octadecyl‐car‐bamoyloxy)‐propyl‐2‐(2‐thiazolio)‐ethylphosphate. These results suggest that DBB primes the responses of human PMNs, and the priming effect is caused by the activation of phospholipase A2—and Ca2+ ‐calmodulin‐pathways, but not by the activation of lipoxygenase, cyclo‐oxygenase and protein kinase C or by the release of platelet activating factor.

Priming effect of 2,3-dibenzylbutane-1,4-diol (mammalian lignan) on superoxide production in human neutrophils

We investigated the effect of 2,3-dibenzylbutane-1,4-diol (DBB), a mammalian lignan, on superoxide production and [Ca2+]i mobilization in human neutrophils. DBB did not generate superoxide production by itself, but enhanced the FMLP or A23187-induced superoxide production in a dose dependent manner. DBB did not influence the OAG-induced superoxide production. The priming effect of DBB was inhibited by W-7 or trifluoroperazine, but not by H-7 or staurosporine. And the priming effect of DBB was observed in the presence or absence of extracellular Ca2+. DBB enhanced the low dose FMLP-induced [Ca2+]i mobilization. These results suggest that the priming effect of DBB in human neutrophils may be caused by the activation of the calcium-calmodulin pathway but not the protein kinase pathway.

The Role of WNT in Rheumatoid Arthritis and its Therapeutic Implication

Rheumatoid arthritis (RA) is a systematic inflammatory and intractable disease, which progressively affects multiple joints. Recent findings strongly suggest a key role of WNT signaling in the disease initiation and progression. In this review, we discuss the role and possibility of treatment by targeting WNT signaling.

Sex-related difference in the effect of aspirin on prostaglandin metabolism in rat platelet and aorta

Abstract The effect of aspirin on the production of the arterial prostacyclin (PGI2)-like substance and platelet malondialdehyde (MDA) was investigated in rats of both sexes. No significant sex difference observed with the arterial PGI2-like substance. But, following the aspirin treatment, the production of the PGI2-like substance was significantly decreased in male rats. There was significant sex difference in the production of platelet MDA before the aspirin treatment. And after the aspirin treatment, platelets of both sexes produced significantly less MDA. It is possible that sex difference in the effect of aspirin is related to the quantitative difference of cyclooxygenase activity between platelets and vasal wall.