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Interleukin (IL)-1beta toxicity to islet beta cells: Efaroxan exerts a complete protection.
J Cell Physiol. 2005 Apr; 203(1):94-102.JC

Abstract

Interleukin (IL)-1beta-treated rat islets of Langerhans were exposed in vitro either to the imidazoline compound, Efaroxan, or to the selective inducible nitric oxide synthase (iNOS) inhibitor, 1400W, in a medium containing a high concentration of glucose (16.7 mmol/L). Our data have evidenced the following: (i) addition of Efaroxan to islet cultures inhibited IL-1beta activation of ICE (cysteine protease IL-1beta converting enzyme) while addition of 1400W did not; (ii) Efaroxan completely inhibited IL-1beta-induced suppression of insulin secretion and induction of iNOS mRNA transcripts, and, in addition, counteracted islet beta-cell protein profile alterations, Bax-cytochrome c translocation, caspase activation, and apoptosis; (iii) 1400W inhibited IL-1beta induction of iNOS, but failed to completely counteract the other cytotoxic effects; (iv) the two compounds, moreover, exerted different effects on manganese superoxide dismutase (MnSOD), in fact, while Efaroxan inhibited the early stimulatory effect of IL-1beta on MnSOD, 1400W did not. Thus, Efaroxan completely protected islet beta cells from damage caused by IL-1beta-induced toxicity, while compound 1400W only inhibited NO radical production without altering the cytokine's cytotoxicity. Our observations have evidenced that suppression of ICE activation is required to counteract IL-1beta-mediated islet beta cell toxicity, and that IL-1beta-induced apoptosis is NO-independent and involves the cytochrome c-mitochondrial pathway.

Authors+Show Affiliations

Department of Experimental Medicine, Section of Histology and Embryology, School of Medicine, 2nd University of Naples, Naples, Italy. gianpaolo.papaccio@unina2.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15389634

Citation

Papaccio, Gianpaolo, et al. "Interleukin (IL)-1beta Toxicity to Islet Beta Cells: Efaroxan Exerts a Complete Protection." Journal of Cellular Physiology, vol. 203, no. 1, 2005, pp. 94-102.
Papaccio G, Graziano A, Valiante S, et al. Interleukin (IL)-1beta toxicity to islet beta cells: Efaroxan exerts a complete protection. J Cell Physiol. 2005;203(1):94-102.
Papaccio, G., Graziano, A., Valiante, S., D'Aquino, R., Travali, S., & Nicoletti, F. (2005). Interleukin (IL)-1beta toxicity to islet beta cells: Efaroxan exerts a complete protection. Journal of Cellular Physiology, 203(1), 94-102.
Papaccio G, et al. Interleukin (IL)-1beta Toxicity to Islet Beta Cells: Efaroxan Exerts a Complete Protection. J Cell Physiol. 2005;203(1):94-102. PubMed PMID: 15389634.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interleukin (IL)-1beta toxicity to islet beta cells: Efaroxan exerts a complete protection. AU - Papaccio,Gianpaolo, AU - Graziano,Antonio, AU - Valiante,Salvatore, AU - D'Aquino,Riccardo, AU - Travali,Salvatore, AU - Nicoletti,Ferdinando, PY - 2004/9/25/pubmed PY - 2005/4/22/medline PY - 2004/9/25/entrez SP - 94 EP - 102 JF - Journal of cellular physiology JO - J Cell Physiol VL - 203 IS - 1 N2 - Interleukin (IL)-1beta-treated rat islets of Langerhans were exposed in vitro either to the imidazoline compound, Efaroxan, or to the selective inducible nitric oxide synthase (iNOS) inhibitor, 1400W, in a medium containing a high concentration of glucose (16.7 mmol/L). Our data have evidenced the following: (i) addition of Efaroxan to islet cultures inhibited IL-1beta activation of ICE (cysteine protease IL-1beta converting enzyme) while addition of 1400W did not; (ii) Efaroxan completely inhibited IL-1beta-induced suppression of insulin secretion and induction of iNOS mRNA transcripts, and, in addition, counteracted islet beta-cell protein profile alterations, Bax-cytochrome c translocation, caspase activation, and apoptosis; (iii) 1400W inhibited IL-1beta induction of iNOS, but failed to completely counteract the other cytotoxic effects; (iv) the two compounds, moreover, exerted different effects on manganese superoxide dismutase (MnSOD), in fact, while Efaroxan inhibited the early stimulatory effect of IL-1beta on MnSOD, 1400W did not. Thus, Efaroxan completely protected islet beta cells from damage caused by IL-1beta-induced toxicity, while compound 1400W only inhibited NO radical production without altering the cytokine's cytotoxicity. Our observations have evidenced that suppression of ICE activation is required to counteract IL-1beta-mediated islet beta cell toxicity, and that IL-1beta-induced apoptosis is NO-independent and involves the cytochrome c-mitochondrial pathway. SN - 0021-9541 UR - https://www.unboundmedicine.com/medline/citation/15389634/Interleukin__IL__1beta_toxicity_to_islet_beta_cells:_Efaroxan_exerts_a_complete_protection_ L2 - https://doi.org/10.1002/jcp.20198 DB - PRIME DP - Unbound Medicine ER -