Exposure to antiepileptic drugs does not alter the functionality of P-glycoprotein in brain capillary endothelial and kidney cell lines.

Several major antiepileptic drugs, including carbamazepine, phenytoin and phenobarbital, induce xenobiotic metabolizing enzymes via activation of nuclear receptors, including pregnane X receptor (NR1I2) and constitutive androstane receptor (NR1I3). Via activation of these xenobiotic sensors, antiepileptic drugs may also induce the expression of efflux transporters such as P-glycoprotein (Pgp) in different tissues, including intestine, liver, kidney and brain. Increased expression of Pgp in brain capillary endothelial cells, which form the blood-brain barrier, could limit the penetration of antiepileptic drugs into the brain and therefore decrease their therapeutic efficacy.

Importance of cholesterol-rich membrane microdomains in the interaction of the S protein of SARS-coronavirus with the cellular receptor angiotensin-converting enzyme 2.

Cholesterol present in the plasma membrane of target cells has been shown to be important for the infection by SARS-CoV. We show that cholesterol depletion by treatment with methyl-beta-cyclodextrin (m beta CD) affects infection by SARS-CoV to the same extent as infection by vesicular stomatitis virus-based pseudotypes containing the surface glycoprotein S of SARS-CoV (VSV-Delta G-S). Therefore, the role of cholesterol for SARS-CoV infection can be assigned to the S protein and is unaffected by other coronavirus proteins.

Analysis of ACE2 in polarized epithelial cells: surface expression and function as receptor for severe acute respiratory syndrome-associated coronavirus.

The primary target of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is epithelial cells in the respiratory and intestinal tract. The cellular receptor for SARS-CoV, angiotensin-converting enzyme 2 (ACE2), has been shown to be localized on the apical plasma membrane of polarized respiratory epithelial cells and to mediate infection from the apical side of these cells. Here, these results were confirmed and extended by including a colon carcinoma cell line (Caco-2), a lung carcinoma cell line (Calu-3) and Vero E6 cells in our analysis.

A novel sorting signal for intracellular localization is present in the S protein of a porcine coronavirus but absent from severe acute respiratory syndrome-associated coronavirus.

Coronaviruses (CoV) mature by a budding process at intracellular membranes. Here we showed that the major surface protein S of a porcine CoV (transmissible gastroenteritis virus) is not transported to the cell surface but is retained intracellularly. Site-directed mutagenesis indicated that a tyrosine-dependent signal (YXXI) in the cytoplasmic tail is essential for intracellular localization of the S protein.