This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sheets, S. M. Articles by Casiano, C. A. Search for Related Content PubMed PubMed Citation Articles by Sheets, S. M. Articles by Casiano, C. A.

 Previous Article  |  Next Article 

Infection and Immunity, October 2006, p. 5667-5678, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.01140-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Gingipains from Porphyromonas gingivalis W83 Synergistically Disrupt Endothelial Cell Adhesion and Can Induce Caspase-Independent Apoptosis

Shaun M. Sheets,^1* Jan Potempa,^2,3 James Travis,³ Hansel M. Fletcher,¹ and Carlos A. Casiano^1,4

Department of Biochemistry and Microbiology, School of Medicine, Loma Linda University, Loma Linda, California,¹ Department of Microbiology, Faculty of Biotechnology, Jagiellonian University, Kraków, Poland,² Department of Biochemistry, University of Georgia, Athens, Georgia,³ Center for Molecular Biology and Gene Therapy, Loma Linda University, Loma Linda, California⁴

Received 18 July 2005/ Returned for modification 12 December 2005/ Accepted 6 July 2006

We have shown previously that gingipains from Porphyromonas gingivalis W83 can induce cell detachment, cell adhesion molecule (CAM) cleavage, and apoptosis in endothelial cells; however, the specific roles of the individual gingipains are unclear. Using purified gingipains, we determined that each of the gingipains can cleave CAMs to varying degrees with differing kinetics. Kgp and HRgpA work together to quickly detach endothelial cells. Interestingly, in the absence of active caspases, both gingipain-active W83 extracts and purified HRgpA and RgpB induce apoptotic morphology, suggesting that the gingipains can induce both caspase-dependent and caspase-independent apoptosis. Using z-VAD-FMK to inhibit Kgp activity and leupeptin to inhibit Rgp activity in gingipain-active W83 extracts, we investigated the relative significance of the synergistic role of the gingipains. z-VAD-FMK or leupeptin delayed, but did not inhibit, cell detachment induced by gingipain-active W83 extracts or purified gingipains. There was partial cleavage of N-cadherin and cleavage of VE-cadherin was not inhibited. Degradation of integrin ß1 was inhibited only in the presence of z-VAD-FMK. These results further clarify the role P. gingivalis plays in tissue destruction occurring in the periodontal pocket.

---

* Corresponding author. Mailing address: Department of Biochemistry and Microbiology, School of Medicine, Loma Linda University, Loma Linda, CA 92350. Phone: (909) 558-4472. Fax: (909) 558-4035. E-mail: ssheets04b{at}llu.edu.

Editor: V. J. DiRita

---

Infection and Immunity, October 2006, p. 5667-5678, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.01140-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Henry, L. G., Sandberg, L., Zhang, K., Fletcher, H. M. (2008). DNA Repair of 8-Oxo-7,8-Dihydroguanine Lesions in Porphyromonas gingivalis. J. Bacteriol. 190: 7985-7993 [Abstract] [Full Text]  
• Bainbridge, B. W., Karimi-Naser, L., Reife, R., Blethen, F., Ernst, R. K., Darveau, R. P. (2008). Acyl Chain Specificity of the Acyltransferases LpxA and LpxD and Substrate Availability Contribute to Lipid A Fatty Acid Heterogeneity in Porphyromonas gingivalis. J. Bacteriol. 190: 4549-4558 [Abstract] [Full Text]