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J. Biol. Chem., Vol. 276, Issue 20, 16667-16673, May 18, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/20/16667    most recent M010774200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Johnstone, R. W. Articles by Smyth, M. J. Search for Related Content PubMed PubMed Citation Articles by Johnstone, R. W. Articles by Smyth, M. J. Social Bookmarking                      What's this?

P-glycoprotein Does Not Protect Cells against Cytolysis Induced by Pore-forming Proteins^*

Ricky W. Johnstone^§, Kellie M. Tainton, Astrid A. Ruefli, Christopher J. Froelich^¶, Loretta Cerruti, Stephen M. Jane^**, and Mark J. Smyth

From the  Peter MacCallum Cancer Institute, Trescowthick Research Laboratories, St. Andrews Place, East Melbourne 3002, Victoria, Australia, the ^¶ Evanston Northwestern Healthcare Research Institute, Evanston, Illinois 60201, and the  Rotary Bone Marrow Research Laboratory, Royal Melbourne Hospital Research Foundation, Parkville 3052, Victoria, Australia

P-glycoprotein (P-gp) is an ATP-dependent drug pump that confers multidrug resistance (MDR). In addition to its ability to efflux toxins, P-gp can also inhibit apoptosis induced by a wide array of cell death stimuli that rely on activation of intracellular caspases for full function. We therefore hypothesized that P-gp may have additional functions in addition to its role in effluxing xenotoxins that could provide protection to tumor cells against a host response. There have been a number of contradictory reports concerning the role of P-gp in regulating complement activation. Given the disparate results obtained by different laboratories and our published results demonstrating that P-gp does not affect cell death induced by another membranolytic protein, perforin, we decided to assess the role of P-gp in regulating cell lysis induced by a number of different pore-forming proteins. Testing a variety of different P-gp-expressing MDR cell lines produced following exposure of cells to chemotherapeutic agents or by retroviral gene transduction in the complete absence of any drug selection, we found no difference in sensitivity of P-gp^+ve or P-gp^ve cells to the pore-forming proteins complement, perforin, or pneumolysin. Based on these results, we conclude that P-gp does not affect cell lysis induced by pore-forming proteins.

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