1.Effects of simulated microgravity on human umbilical vein endothelial cell angiogenesis and role of the PI3K-Akt-eNOS signal pathway.
Shi F1, Wang YC, Zhao TZ, Zhang S, Du TY, Yang CB, Li YH, Sun XQ. PLoS One. 2012;7(7):e40365. doi: 10.1371/journal.pone.0040365. Epub 2012 Jul 13.
Endothelial cells are very sensitive to microgravity and the morphological and functional changes in endothelial cells are believed to be at the basis of weightlessness-induced cardiovascular deconditioning. It has been shown that the proliferation, migration, and morphological differentiation of endothelial cells play critical roles in angiogenesis. However, the influence of microgravity on the ability of endothelial cells to foster angiogenesis remains to be explored in detail. In the present study, we used a clinostat to simulate microgravity, and we observed tube formation, migration, and expression of endothelial nitric oxide synthase (eNOS) in human umbilical vein endothelial cells (HUVEC-C). Specific inhibitors of eNOS and phosphoinositide 3-kinase (PI3K) were added to the culture medium and gravity-induced changes in the pathways that mediate angiogenesis were investigated. After 24 h of exposure to simulated microgravity, HUVEC-C tube formation and migration were significantly promoted.
2.Functional roles of arginine during the peri-implantation period of pregnancy. III. Arginine stimulates proliferation and interferon tau production by ovine trophectoderm cells via nitric oxide and polyamine-TSC2-MTOR signaling pathways.
Wang X1, Burghardt RC2, Romero JJ3, Hansen TR3, Wu G1, Bazer FW4. Biol Reprod. 2015 Mar;92(3):75. doi: 10.1095/biolreprod.114.125989. Epub 2015 Feb 4.
In mammal species, arginine is a multifunctional amino acid required for survival, growth, and development of conceptuses (embryo/fetus and associated extraembryonic membranes) during the peri-implantation period of pregnancy. However, functional roles of arginine with respect to it being a substrate for production of nitric oxide (NO) and polyamines on trophectoderm cell proliferation and function remain largely unknown. To systematically assess roles of arginine in conceptus development and its effect on interferon tau (IFNT) production for pregnancy recognition signaling in ruminants, an established ovine trophectoderm (oTr1) cell line isolated from Day-15 ovine conceptuses were used to determine their response to arginine, putrescine, and NO donors, as well as their associated inhibitors. Arginine at physiological concentration (0.2 mM) stimulated maximum oTr cell proliferation (increased 2.0-fold at 48 h and 2.6-fold at 96 h; P < 0.
3.Fasudil and ozagrel in combination show neuroprotective effects on cerebral infarction after murine middle cerebral artery occlusion.
Koumura A1, Hamanaka J, Kawasaki K, Tsuruma K, Shimazawa M, Hozumi I, Inuzuka T, Hara H. J Pharmacol Exp Ther. 2011 Jul;338(1):337-44. doi: 10.1124/jpet.110.177675. Epub 2011 Apr 14.
Rho kinase (ROCK), one of the serine/threonine kinases, is involved in pathologic conditions, and its activation causes neuronal cell death. Fasudil, a selective ROCK inhibitor, has been reported to cause increased cerebral blood flow (CBF) in the ischemic brain and protect against neuronal cell death by inhibiting ROCK. Ozagrel, a thromboxane A(2) synthase inhibitor, inhibits platelet aggregation and causes vasodilatation, thereby increasing CBF in cerebral thrombosis. The present study evaluates the combination therapy of fasudil and ozagrel on focal brain ischemia induced by middle cerebral artery occlusion (MCAO) in mice. Each monotherapy of fasudil at 10 mg/kg i.p. and ozagrel at 30 mg/kg i.p. significantly reduced cerebral infarction. The combination therapy of fasudil (3 mg/kg i.p.) and ozagrel (10 mg/kg i.p.), which are noneffective doses, resulted in reduction of cerebral infarction, and the protective effect was observed up to 5 min, but not 3 h, after reperfusion.
4.Synthesis and some properties and antitumor effects of the actinomycin lactam analog, (di(1-L-alpha, beta-diaminopropionic))actinomycin D1.
Moore S, Patel RP, Atherton E, Kondo M, Meienhofer J. J Med Chem. 1976 Jun;19(6):766-72.
A lactam analog of actinomycin D (AMD) has been synthesized as a potential antitumor chemotherapeutic agent. Both L-threonine residues were replaced by L-alpha,beta-diaminopropionic acid. Starting with Nalpha-benzyloxycarbonyl-Nbeta-tert-butyloxycarbonyl-L-alpha,beta-diaminopropionic acid methyl ester hydrochloride the linear intermediate Nalpha-benzyloxycarbonyl-Nbeta-(tert-butyloxycarbonylsarcosyl-L-N-methylvalyl)-L-alpha,beta-diaminopropionyl-D-valyl-L-proline p-nitrophenyl ester was prepared by conventional methods of peptide synthesis in solution. Selective cleavage of the Nbeta-tert-butyloxycarbonyl group and lactam formation afforded the desired cyclic pentapeptide derivative. The chromophore precursor, Nalpha-(2-nitro-3-benzyloxy-4-methylbenzoyl) substituent, was introduced via its symmetric anhydride. Catalytic reduction followed by ferricyanide-mediated phenoxazinone formation provided the lactam analog, [di(1'-L-alpha,beta-diaminopionic acid)]actinomycin D ([Dpr1]2-AMD).
