Pim-1 Kinase Protects P-Glycoprotein from Degradation and Enables Its Glycosylation and Cell Surface Expression

Previous studies have demonstrated that mitomycin C (MMC) and other DNA cross-linking agents can suppress MDR1 (multidrug resistance 1) gene expression and subsequent functional P-glycoprotein (Pgp) expression, whereas doxorubicin and other anthracyclines increase MDR1 gene expression. In the present study, with stably transfected Madin–Darby canine kidney C7 epithelial cells expressing a human Pgp tagged with green fluorescent protein under the proximal human MDR1 gene promoter, we demonstrated that MMC and doxorubicin have differential effects on Pgp expression and function. Doxorubicin caused a progressive increase in the cell-surface expression of Pgp and function. In contrast, MMC initially increased plasma membrane expression and function at a time when total cellular Pgp was constant and Pgp mRNA expression had been shown to be suppressed. This was followed by a rapid and sustained decrease in cell-surface expression at later times, presumably as a consequence of the initial decrease in mRNA expression. These studies imply that there are at least two independent chemosensitive steps that can alter Pgp biogenesis: one at the level of mRNA transcription and the other at the level of Pgp trafficking. Understanding the combined consequences of these two mechanisms might lead to novel chemotherapeutic approaches to overcoming drug resistance in human cancers by altering either Pgp mRNA expression or trafficking to the membrane.

Download Full-text

Faculty Opinions recommendation of Assembly and cell surface expression of TAP-independent, chloroquine-sensitive and interferon-gamma-inducible class I MHC complexes in transformed fibroblast cell lines are regulated by tapasin.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1009214.121258 ◽

2002 ◽

Author(s):

Tim Elliott

Keyword(s):

Cell Surface ◽

Cell Lines ◽

Interferon Gamma ◽

Fibroblast Cell ◽

Surface Expression ◽

Class I ◽

Cell Surface Expression ◽

Class I Mhc ◽

Fibroblast Cell Lines

Download Full-text

Faculty Opinions recommendation of Mechanism of cell surface expression of the Streptococcus mitis platelet binding proteins PblA and PblB.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1082761.535676 ◽

2007 ◽

Author(s):

Tim Mitchell

Keyword(s):

Cell Surface ◽

Binding Proteins ◽

Surface Expression ◽

Cell Surface Expression ◽

Streptococcus Mitis ◽

Platelet Binding

Download Full-text

Persistent HIV Transcription Induces Sialyl-Lewis-X Glyco-Antigen Cell-Surface Expression

SSRN Electronic Journal ◽

10.2139/ssrn.3565035 ◽

2020 ◽

Author(s):

Florent Colomb ◽

Leila B. Giron ◽

Leticia Kuri Cervantes ◽

Tongcui Ma ◽

Samson Adeniji ◽

...

Keyword(s):

Cell Surface ◽

Surface Expression ◽

Sialyl Lewis X ◽

Cell Surface Expression ◽

Lewis X ◽

Hiv Transcription ◽

Sialyl Lewis

Download Full-text

Influence of β-D-mannuronic acid, as a new member of non-steroidal anti-inflammatory drugs family, on expression pattern of chemokines and their receptors in rheumatoid arthritis

Current Drug Discovery Technologies ◽

10.2174/1570163816666191023103118 ◽

2019 ◽

Vol 16 ◽

Author(s):

Mona Aslani ◽

Arman Ahmadzadeh ◽

Zahra Aghazadeh ◽

Majid Zaki-Dizaji ◽

Laleh Sharifi ◽

...

Keyword(s):

Cell Surface ◽

Mrna Expression ◽

Surface Expression ◽

Phase Iii ◽

Cell Surface Expression ◽

Optimum Dose ◽

High Dose ◽

Mannuronic Acid ◽

Anti Inflammatory ◽

High Doses

Background: : Based on the encouraging results of phase III clinical trial of β-D-mannuronic acid (M2000) (as a new anti-inflammatory drug) in patients with RA, in this study, we aimed to evaluate the effects of this drug on the expression of chemokines and their receptors in PBMCs of RA patients. Methods:: PBMCs of RA patients and healthy controls were separated and the patients' cells were treated with low, moderate and high doses (5, 25 and 50 μg/mL) of M2000 and optimum dose (1 μg/mL) of diclofenac, as a control in RPMI-1640 medium. Real-time PCR was used for evaluating the mRNA expression of CXCR3, CXCR4, CCR2, CCR5 and CCL2/MCP-1. Cell surface expression of CCR2 was investigated using flow cytometry. Results:: CCR5 mRNA expression reduced significantly, after treatment of the patients' cells with all three doses of M2000 and optimum dose of diclofenac. CXCR3 mRNA expression down-regulated significantly followed by treatment of these cells with moderate and high doses of M2000 and optimum dose of diclofenac. CXCR4 mRNA expression declined significantly after treatment of these cells with moderate and high doses of M2000. CCL2 mRNA expression significantly reduced only followed by treatment of these cells with high dose of M2000, whereas, mRNA and cell surface expressions of CCR2 diminished significantly followed by treatment of these cells with high dose of M2000 and optimum dose of diclofenac. Conclusion:: According to our results, M2000 through the down-regulation of chemokines and their receptors may restrict the infiltration of immune cells into the synovium.

Download Full-text