Biomedical subjects

Chiara Zoia

Publications and source records attributed to Chiara Zoia.

3 recordsLinked to original sources

PubMed2005

Enhanced GM1 ganglioside catabolism in cultured fibroblasts from Alzheimer patients.

The metabolic processing of GM1 ganglioside, exogenously administered to cultured skin fibroblasts, was investigated on cells obtained from patients affected with Alzheimer disease, in comparison with age-matched control subjects. Cultured fibroblasts were incubated with GM1 ganglioside, [(3)H]-radiolabelled at the sphingosine moiety. It was observed that the extent of tritiated GM2 and GM3 ganglioside formation was higher in AD fibroblasts than in control cells. The activity of acidic beta-D-galactosidase, responsible of GM1 hydrolysis to GM2 within lysosomes, assayed in vitro on cell lysates, was increased in AD fibroblasts in comparison with control cells. These data suggest that up-regulation of lysosomal enzymes could be responsible of the enhanced GM1 catabolism in AD fibroblasts. Finally, it was found that the extent of GM1 hydrolysis in AD fibroblasts was inversely correlated with the mini-mental score index of patients. The increased hydrolysis rate of sphingolipids could be taken as peripheral hallmark of Alzheimer's disease patients.

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PubMed2004

Impairment of glutamate transport and increased vulnerability to oxidative stress in neuroblastoma SH-SY5Y cells expressing a Cu,Zn superoxide dismutase typical of familial amyotrophic lateral sclerosis.

Human neuroblastoma SH-SY5Y cells transfected with either familial amyotrophic lateral sclerosis-typical G93A mutant or wild-type copper/zinc superoxide dismutase were compared to untransfected cells in term of glutamate transport. Vmax of glutamate uptake was reduced in mutant cells, with no change in Km. No difference in EAAT1, EAAT2 and EAAT3 glutamate transporter mRNAs and immunoreactive proteins was found, suggesting that one or more transporters are functionally inactivated, possibly due to increased oxidative stress induced by the G93A mutation. Mutant cells showed a marked sensitivity to oxidants, resulting in a more pronounced reduction of glutamate uptake. Short-term antioxidant treatment did not reverse the impairment of glutamate uptake in G93A cells. Interestlingly, N-acetylcysteine was partially effective in preventing glutamate uptake reduction due to exogenous oxidative insults. Since the inhibition of the EAAT2 transporter subtype had no effect on glutamate re-uptake in this model, our study suggests an impaired function of the EAAT1/3 transporter subtypes, possibly due to oxidative inactivation, in the presence of mutant copper/zinc superoxide dismutase. Therefore, this model might prove to be a valuable tool to study the effects of mutant copper/zinc superoxide dismutase associated with amyotrophic lateral sclerosis on glutamate transport in neuronal cells, without the specific contribution of glial cells. These findings might lead to the identification of new therapeutic strategies aimed at preventing the damage associated with ALS.

Amino Acid Transport System X-AG↗

PubMed2004

Glutamate transporters in platelets: EAAT1 decrease in aging and in Alzheimer's disease.

Platelets release glutamate upon activation and are an important clearance system of the amino acid from blood, through high-affinity glutamate uptake, similar to that described in brain synaptosomes. Since platelet glutamate uptake is decreased in neurodegenerative disorders, we performed a morphological and molecular characterization of platelet glutamate transporters. The three major brain glutamate transporters EAAT1, EAAT2 and EAAT3 are expressed in platelets, with similar molecular weight, although at lower density than brain. A Na(+)-dependent-high-affinity glutamate uptake was competitively inhibited by known inhibitors but not by dihydrokainic acid, suggesting platelet EAAT2 does not play a major role in glutamate uptake at physiological conditions. We observed decreased glutamate uptake V(max), without modification of transporter affinity, in aging, which could be linked to the selective decrease of EAAT1 expression and mRNA. Moreover, in AD patients we found a further EAAT1 reduction compared to age-matched controls, which could explain the decrease of platelet uptake previously described. Platelet glutamate transporters may be used as peripheral markers to investigate the role of glutamate in patients with neuropsychiatric disorders.

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