Proteomic analysis of liver in mice with different susceptibilities to fluorosis

• Ano de defesa: 2018
• Autor(a) principal: Khan, Zohaib Nisar
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: eng
• Instituição de defesa: Biblioteca Digitais de Teses e Dissertações da USP
• Palavras-chave em Português: Estresse oxidativo; Fígado; Fluoreto; Fluoride; Fluorose; Fluorosis; Genetic susceptibility; Liver; Oxidative stress; Proteômica; Proteomics; Suscetibilidade genética
• Link de acesso: https://www.teses.usp.br/teses/disponiveis/25/25149/tde-16122021-162623/

Fluoride (F) is a potent anti-cariogenic element, but only an appropriate dose is effective to have therapeutic action, else systemic toxicity may be observed. Additionally, two factors, amount of F and time of exposure, drive its action. Surprisingly, the susceptibility to toxic effects of F is genetically determined. The present study identified the effects of F on the liver proteome of mice susceptible (A/J) or resistant (129P3/J) to the effects of F. Weanling male A/J (n=6) and 129P3/J mice (n=6) were housed in pairs and assigned to three groups given low-F diet and drinking water containing 0, 15 or 50 ppm F for 7 weeks. Liver proteome profiles were examined using nano-LC-ESI-MS/MS. Protein function was classified by GO biological process (Cluego v2.0.7 + Clupedia v1.0.8). Difference in expression among the groups was determined using the PLGS software. In the control group (0 ppm F), most proteins with fold change were increased in A/J mice. Precisely the proteins related to energy flux and oxidative stress were quite significant in this context, suggesting the high susceptibility of these mice to the effects of F, since the exposure also induces oxidative stress. Treatment with the lower F concentration provoked more pronounced alterations in fold change in liver proteins in comparison to the treatment with the higher F concentration. Strikingly, most of the proteins with fold change upon following 15 ppm F treatment, were increased in the A/J mice compared with their 129P3/J counterparts, thus suggesting attempt of the former to fight against the toxic effects of F. With respect to 50 ppm F, most proteins with fold change were decreased in the A/J mice compared with their 129P3/J counterparts, especially proteins related to oxidative stress and protein folding, which might be related to the higher susceptibility of the A/J animals to the deleterious effects of F. Our findings can provide new insights into the molecular mechanisms underlying genetic susceptibility to fluorosis by indicating key protein players which need to be better addressed in future experimental studies.