Next Article in Journal
Previous Article in Journal
Previous Article in Special Issue
Int. J. Mol. Sci. 2014, 15(4), 6843-6856; doi:10.3390/ijms15046843
Article

Block of the Mevalonate Pathway Triggers Oxidative and Inflammatory Molecular Mechanisms Modulated by Exogenous Isoprenoid Compounds

1
, 2
, 2
, 1
, 2
, 1,2
, 2
 and 2,*
Received: 28 February 2014; in revised form: 3 April 2014 / Accepted: 4 April 2014 / Published: 22 April 2014
(This article belongs to the Special Issue Redox Signaling in Biology and Patho-Biology)
View Full-Text   |   Download PDF [1583 KB, uploaded 19 June 2014]   |   Browse Figures
Abstract: Deregulation of the mevalonate pathway is known to be involved in a number of diseases that exhibit a systemic inflammatory phenotype and often neurological involvements, as seen in patients suffering from a rare disease called mevalonate kinase deficiency (MKD). One of the molecular mechanisms underlying this pathology could depend on the shortage of isoprenoid compounds and the subsequent mitochondrial damage, leading to oxidative stress and pro-inflammatory cytokines’ release. Moreover, it has been demonstrated that cellular death results from the balance between apoptosis and pyroptosis, both driven by mitochondrial damage and the molecular platform inflammasome. In order to rescue the deregulated pathway and decrease inflammatory markers, exogenous isoprenoid compounds were administered to a biochemical model of MKD obtained treating a murine monocytic cell line with a compound able to block the mevalonate pathway, plus an inflammatory stimulus. Our results show that isoprenoids acted in different ways, mainly increasing the expression of the evaluated markers [apoptosis, mitochondrial dysfunction, nucleotide-binding oligomerization-domain protein-like receptors 3 (NALP3), cytokines and nitric oxide (NO)]. Our findings confirm the hypothesis that inflammation is triggered, at least partially, by the shortage of isoprenoids. Moreover, although further studies are necessary, the achieved results suggest a possible role for exogenous isoprenoids in the treatment of MKD.
Keywords: isoprenoids; mevalonate; inflammation; phytol; lycopene isoprenoids; mevalonate; inflammation; phytol; lycopene
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Export to BibTeX |
EndNote


MDPI and ACS Style

Tricarico, P.M.; Kleiner, G.; Valencic, E.; Campisciano, G.; Girardelli, M.; Crovella, S.; Knowles, A.; Marcuzzi, A. Block of the Mevalonate Pathway Triggers Oxidative and Inflammatory Molecular Mechanisms Modulated by Exogenous Isoprenoid Compounds. Int. J. Mol. Sci. 2014, 15, 6843-6856.

AMA Style

Tricarico PM, Kleiner G, Valencic E, Campisciano G, Girardelli M, Crovella S, Knowles A, Marcuzzi A. Block of the Mevalonate Pathway Triggers Oxidative and Inflammatory Molecular Mechanisms Modulated by Exogenous Isoprenoid Compounds. International Journal of Molecular Sciences. 2014; 15(4):6843-6856.

Chicago/Turabian Style

Tricarico, Paola M.; Kleiner, Giulio; Valencic, Erica; Campisciano, Giuseppina; Girardelli, Martina; Crovella, Sergio; Knowles, Alessandra; Marcuzzi, Annalisa. 2014. "Block of the Mevalonate Pathway Triggers Oxidative and Inflammatory Molecular Mechanisms Modulated by Exogenous Isoprenoid Compounds." Int. J. Mol. Sci. 15, no. 4: 6843-6856.



Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert