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Hughes FM, Corn AG, Nimmich AR, et al. Cyclophosphamide Induces an Early Wave of Acrolein-Independent Apoptosis in the Urothelium. Adv Biosci Biotechnol. 2013;4(88)doi: 10.4236/abb.2013.48A2002.
Hughes, F. M., Corn, A. G., Nimmich, A. R., Pratt-Thomas, J. D., & Purves, J. T. (2013). Cyclophosphamide Induces an Early Wave of Acrolein-Independent Apoptosis in the Urothelium. Advances in bioscience and biotechnology (Print), 4(88), . https://doi.org/10.4236/abb.2013.48A2002
Hughes, Francis M, et al. "Cyclophosphamide Induces an Early Wave of Acrolein-Independent Apoptosis in the Urothelium." Advances in bioscience and biotechnology (Print) vol. 4,88 (2013). doi: https://doi.org/10.4236/abb.2013.48A2002
Hughes FM, Corn AG, Nimmich AR, Pratt-Thomas JD, Purves JT. Cyclophosphamide Induces an Early Wave of Acrolein-Independent Apoptosis in the Urothelium. Adv Biosci Biotechnol. 2013 Aug;4(88). doi: 10.4236/abb.2013.48A2002. PMID: 24353901; PMCID: PMC3864667.
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Adv Biosci Biotechnol. 2013 Aug;4(88). doi: 10.4236/abb.2013.48A2002.

Cyclophosphamide Induces an Early Wave of Acrolein-Independent Apoptosis in the Urothelium.

Advances in bioscience and biotechnology (Print)

Francis M Hughes, Alexa G Corn, Andrew R Nimmich, Jeffery D Pratt-Thomas, J Todd Purves

Affiliations

  1. Department of Urology, Medical University of South Carolina. Charleston, SC.
  2. Department of Urology, Medical University of South Carolina. Charleston, SC ; Department of Pediatrics, Medical University of South Carolina. Charleston, SC ; Department of Regenerative Medicine and Cell Biology. Medical University of South Carolina. Charleston, SC.

PMID: 24353901 PMCID: PMC3864667 DOI: 10.4236/abb.2013.48A2002

Abstract

PURPOSE: Hemorrhagic cystitis (HC or bladder inflammation) affects a significant number of patients undergoing cyclophosphamide (CP) chemotherapy despite treatment with 2-mercapto

MATERIALS AND METHODS: Apoptosis in urothelium (caspase-3/7 activity and Poly (ADP-ribosyl) polymerase (PARP) cleavage) was measured following CP administration (80 mg/kg). Sodium 2-mercaptoethane sulfonate (Mesna) was used to mask acrolein's effect. An IL-1β receptor antagonist and a cell-permeable caspase-1 inhibitor were used to assess the involvement of IL-1β and caspase-1, respectively.

RESULTS: Two waves of apoptosis were detected following CP administration, one peaking at 2 h and a second at 48 h. The first wave was independent of acrolein. Caspase-1 was also active at 2 h and activation of caspase-3/7 was blocked by a caspase-1 inhibitor but not an IL-1β receptor antagonist suggesting the direct activation of caspase-3/7 by caspase-1 without the need for IL-1β as an intermediate.

CONCLUSIONS: Our results indicate that CP initiates an early, acrolein-independent wave of apoptosis that results from direct cleavage of caspase-3/7 by caspase-1.

Keywords: Apoptosis; Bladder; Cyclophosphamide; Cystitis; Urothelium

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