Role of peroxiredoxin III in the pathogenesis of pre-eclampsia as evidenced in mice

As a member of peroxiredoxin (Prx) family, PrxIII has been demonstrated to play an important role in scavenging intracellular reactive oxygen species (ROS). Since PrxIII knockout mice exhibited oxidative stress in placentas resembling pathophysiologic changes in placentas of human pre-eclampsia, we measured blood pressure through the carotid artery and detected oxidative status by western blotting in pregnant mice. We did not notice hypertension in pregnant PrxIII knockout mice as compared with wild-type littermates, although endothelin-1 was overexpressed in PrxIII-deficient placentas. Our results indicate that PrxIII is not involved in pre-eclamptic development. Instead, PrxIII is an indispensable antioxidant in placentas where oxidative stress exists

A mouse bone marrow stromal cell line, TBR-B, shows inducible expression of smooth muscle-specific genes

AbstractWe established an in vitro culture system which mimicked the differentiation pathway of smooth muscle cell, using TBR-B, a bone marrow stromal cell line derived from transgenic mice harboring temperature-sensitive SV40 large T-antigen gene. TBR-B cells have the potential to express smooth muscle-specific genes including h1-calponin, h-caldesmon, SM22α and α-actin, only after cultured in the differentiation medium for 2 weeks. The differentiation state of TBR-B was well controlled by using different culture medium. Using this cell line, we also found that ascorbic acid is a potent factor inducing the expression of h1-calponin and α-actin. TBR-B cells will serve as a useful tool for elucidating the regulatory mechanisms of smooth muscle-specific gene expression, and for identifying compounds that regulate the differentiation state of vascular smooth muscle cells

Effects of hangeshashinto on butyrate-induced cell death in murine colonic epithelial cell

Recent findings demonstrated that a significant number of Fusobacterium varium was identified in the mucosa of patients with ulcerative colitis (UC) (Ohkusa et al., J. Gastroenterol. Hepatol., 17, 849-853, 2002), and it has been suggested that the butyrate produced by F. varium is involved in the pathogenesis of UC (Ohkusa et al., Gut, 52, 79-83, 2003). In the screening of Kampo formulas to protect butyrate-induced death of murine colonic epithelial cells MCE301 as an in vitro model of UC, it was found that the hangeshashinto (HST, Banxia Xiexin Tang in Chinese) and its related Kampo formulas showed the potent inhibitory activity against butyrate-induced cell death. Of the components of the formulation of HST, only decocted extract of Coptidis Rhizoma showed the potent activity. The inhibitory effect of HST extract was disappeared after removal of Coptidis Rhizoma from the formula of HST. By bioassay guided fractionation of Coptidis Rhizoma extract, and HPLC analysis of the active fraction in comparison with standard samples, berberine was identified as one of active ingredients of Coptidis Rhizoma extract. These results suggest that berberine in HST and related formulas inhibits the butyrate-induced colonic epithelial cell death. HST and its related formulations have been clinically used for the treatment of UC. The data presented here may partly explain the mechanism of clinical effectiveness of HST and its related Kampo formulas on treatment of UC. 酪酸で誘発されるマウス結腸上皮細胞株MCE301細胞の細胞死をin vitroの潰瘍性大腸炎モデルとして用いて検討を行った。44種類の漢方薬を対象にスクリーニングを行った結果,半夏瀉心湯およびその関連処方4種が酪酸による細胞死を抑制することを見いだした。活性の観察された漢方方剤の多くは臨床的に潰瘍性大腸炎の治療に応用される漢方薬であった。半夏瀉心湯エキスの活性は,構成生薬である黄連を除くことにより消失したことから,黄連が活性発現に重要な構成生薬であると考えられた。黄連エキス中の活性物質について検討した結果,活性物質はベルベリンであることが明らかとなった。潰瘍性大腸炎に対する半夏瀉心湯の臨床的な効果には,酪酸によって誘発される結腸上皮細胞死に対するベルベリンの抑制作用が関与する可能性が示唆された