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2018 ; 8
(6
): 540-546
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Neuronal damage and shortening of lifespan in C elegans by peritoneal dialysis
fluid: Protection by glyoxalase-1
#MMPMID29805788
Schlotterer A
; Pfisterer F
; Kukudov G
; Heckmann B
; Henriquez D
; Morath C
; Krämer BK
; Hammes HP
; Schwenger V
; Morcos M
Biomed Rep
2018[Jun]; 8
(6
): 540-546
PMID29805788
show ga
Glucose and glucose degradation products (GDPs), contained in peritoneal dialysis
(PD) fluids, contribute to the formation of advanced glycation end-products
(AGEs). Local damaging effects, resulting in functional impairment of the
peritoneal membrane, are well studied. It is also supposed that detoxification of
AGE precursors by glyoxalase-1 (GLO1) has beneficial effects on GDP-mediated
toxicity. The aim of the current study was to analyze systemic detrimental
effects of PD fluids and their prevention by glyoxlase-1. Wild-type and
GLO1-overexpressing Caenorhabditis elegans (C. elegans) were cultivated in the
presence of low- and high-GDP PD fluids containing 1.5 or 4% glucose. Lifespan,
neuronal integrity and neuronal functions were subsequently studied. The higher
concentrations of glucose and GDP content resulted in a decrease of maximum
lifespan by 2 (P<0.01) and 9 days (P<0.001), respectively. Exposure to low- and
high-GDP fluids caused reduction of neuronal integrity by 34 (P<0.05) and 41%
(P<0.05). Cultivation of animals in the presence of low-GDP fluid containing 4%
glucose caused significant impairment of neuronal function, reducing relative and
absolute head motility by 58.5 (P<0.01) and 56.7% (P<0.01), respectively; and
relative and absolute tail motility by 55.1 (P<0.05) and 55.0% (P<0.05),
respectively. Taken together, GLO1 overexpression protected from glucose-induced
lifespan reduction, neurostructural damage and neurofunctional damage under
low-GDP-conditions. In conclusion, both glucose and GDP content in PD fluids have
systemic impact on the lifespan and neuronal integrity of C. elegans.
Detoxification of reactive metabolites by GLO1 overexpression was sufficient to
protect lifespan, neuronal integrity and neuronal function in a low-GDP
environment. These data emphasize the relevance of the GLO1 detoxifying pathway
as a potential therapeutic target in the treatment of reactive
metabolite-mediated pathologies.
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