Febs Letters

doi: 10.1016/S0014-5793(05)01441-9pmid: N/A

doi: 10.1016/S0014-5793(05)01407-9pmid: N/A

Schatz, Gottfried

doi: 10.1016/j.febslet.2005.11.025pmid: N/A

Chow, Ken Y.C.; Yeung, Yin Shan; Hon, Chung Chau; Zeng, Fanya; Law, Ka Man; Leung, Frederick C.C.

doi: 10.1016/j.febslet.2005.10.065pmid: 16310778

The pro‐apoptotic properties of severe acute respiratory syndrome coronavirus (SARS‐CoV) structural proteins were studied in vitro. By monitoring apoptosis indicators including chromatin condensation, cellular DNA fragmentation and cell membrane asymmetry, we demonstrated that the adenovirus‐mediated over‐expression of SARS‐CoV spike (S) protein and its C‐terminal domain (S2) induce apoptosis in Vero E6 cells in a time‐ and dosage‐dependent manner, whereas the expression of its N‐terminal domain (S1) and other structural proteins, including envelope (E), membrane (M) and nucleocapsid (N) protein do not. These findings suggest a possible role of S and S2 protein in SARS‐CoV induced apoptosis and the molecular pathogenesis of SARS.

Christman, Shelly A.; Kong, Byung-Whi; Landry, Megan M.; Kim, Hyunggee; Foster, Douglas N.

doi: 10.1016/j.febslet.2005.10.066pmid: 16313905

We have established a spontaneously immortalized chicken embryo fibroblast (CEF) cell line (SC‐1) that has been in continuous culture for more than three years. This is only the second report of a spontaneously immortalized reverse transcriptase (RT)‐negative chicken cell line. The SC‐1 cells emerged from crisis (at about passage 29–31) with a slower growth rate than primary cells. Passage 50 SC‐1 cells expressed similar levels of p53 mRNA, but slightly lower levels of p53 protein than passage 6 CEF cells. By passage 120, p53 mRNA levels were significantly decreased in the SC‐1 cells, while protein levels were slightly increased compared to passage 6 CEF cells. However, functional analysis of p53 revealed reduced activity in later passage SC‐1 cells. Other p53‐related genes including p21WAF1, p27Kip1, MDM‐2, and the p16INK4a alternate reading frame (ARF) sequence showed similar patterns of differential mRNA expression. Levels of p15INK4b mRNA and protein were dramatically decreased in SC‐1 cells, suggesting that the Rb pathway also has been compromised. Telomerase expression was undetectable in SC‐1 cells. Fluorescence‐activated cell sorting analysis showed that SC‐1 and primary cells contained a similar proportion of G0/G1 phase cells, unlike the only other spontaneously immortalized chicken cell line (DF‐1). The present study suggests that alterations in the p53 and Rb pathways cause fluctuations in expression levels of important cell‐cycle regulatory genes during crucial transition periods as the SC‐1 spontaneously immortalized chicken fibroblast cells progress toward becoming a fully committed cell line.

Pan, Tianhong; Li, Xinqun; Xie, Wenjie; Jankovic, Joseph; Le, Weidong

doi: 10.1016/j.febslet.2005.10.067pmid: 16313906

Valproic acid (VPA), an anticonvulsant and mood‐stabilizing drug, has been reported to exert neuroprotection against a variety of insults. We now show that VPA attenuates rotenone (a potent complex I inhibitor)‐induced apoptosis through the induction of heat shock protein 70, which may interact with apoptotic‐protease‐activating factor 1. Activation of p‐Akt, p‐Bcl‐2, as well as p‐Erk1/2 by VPA may be co‐contributors to the protection.

Matsusaka, Satoshi; Wakabayashi, Ichiro

doi: 10.1016/j.febslet.2005.10.068pmid: 16310780

The purpose of the present study was to investigate whether 5‐hydroxytryptamine (5‐HT, serotonin) affects migration of vascular endothelial cells. 5‐HT significantly enhanced migration of human aortic endothelial cells (HAECs), and this enhancement was completely inhibited by GR 55562, a 5‐HT1 receptor antagonist, and fluoxetine, a 5‐HT transporter inhibitor, but was not affected by ketanserin, a 5‐HT2 receptor antagonist. 5‐HT stimulation increased RhoA and ERK activity of HAECs, and inhibitors of RhoA (Y‐27632 and H‐1152) and inhibitors of MEK (U0126 and PD98059) abolished the 5‐HT‐induced increase in migration velocity. Inhibition of Rho kinase by Y‐27632 blocked stress fiber formation and rear release of HAECs. Thus, 5‐HT has a potent enhancing action on migration of HAECs through activating the RhoA and ERK pathways following 5‐HT1 receptor stimulation.

Espinoza-Fonseca, L. Michel; Trujillo-Ferrara, José G.

doi: 10.1016/j.febslet.2005.10.069pmid: 16310776

Staurosporine and four staurosporine derivatives were docked on the rhodopsin‐based homology model of the M1 muscarinic acetylcholine receptor in order to localize the possible allosteric sites of this receptor. It was found that there were three major allosteric sites, two of which are located at the extracellular face of the receptor, and one in the intracellular domain of the receptor. In the present study, the localization of these binding sites is described for the first time. The present study confirms the existence of multiple allosteric sites on the M1 muscarinic receptor, and lays the ground for further experimental and computational analysis to better understand how muscarinic receptors are modulated via their allosteric sites. These findings will also help to design and develop novel drugs acting as allosteric modulators of the M1 receptor, which can be used in the treatment of the Alzheimer's disease.

Koike, Chika; Moore, Rick; Negishi, Masahiko

doi: 10.1016/j.febslet.2005.10.070pmid: 16310787

The nuclear receptor constitutive active/androstane receptor CAR is a drug‐sensing transcription factor. Upon activation by various drugs such as phenobarbital (PB), CAR translocates from the cytoplasm into the nucleus to regulate the genes that encode enzymes and proteins involved in hepatic metabolism. Here, we have shown the presence of CAR at the cell membrane of mouse livers, using Car +/+ and Car −/− mice. Levels of the cell membrane CAR increased after PB treatment. The CAR exists as a large approximately 160 kDa complex. Thus, CAR undergoes PB‐induced translocation to the cell membrane, indicating that CAR may exert a non‐genomic action.

Youm, Jung Won; Kim, Hee; Han, Jee Hye Lo; Jang, Chang Hwan; Ha, Hee Jin; Mook-Jung, Inhee; Jeon, Jae Heung; Choi, Cheol Yong; Kim, Young Ho; Kim, Hyun Soon; Joung, Hyouk

doi: 10.1016/j.febslet.2005.11.003pmid: 16310782