A link between glutamine metabolism and selective neuronal vulnerability in the hippocampus

• Autorzy: Bochomulski P. , Krupska O. , Klimczak P. , Hilgier W. , Zablocka B. , Beresewicz M.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: The brain has developed several endogenous mechanisms to protect itself from the harm ful consequences of ischemia/reperfusion (I/R) injury. Understanding of such mechanisms may be important for the development of new neuroprotective therapies. In a gerbil model of cerebral ischemia, 5 min-ischemia results in selective, delayed neuronal death in the hippocampal CA1 region, while CA2‑4 and the DG remains relatively resistant. We have shown that I/R‑induced translocation of protein kinase C beta II (PKCβII) from cytoplasm to mitochondria only in CA2‑4 and the DG is relevant for ischemia‑resistance of these regions. The exact mechanism remains unknown. AIM(S): The aim of the study was to investigate the role of kidney‑type glutaminase (GLS1), identified as a potential PKCβII partner, in PKCβII‑mediated neuroprotection. METHOD(S): Reciprocal co-immunoprecipitation method showed that of the two GLS1 isoforms, it is GAC not KGA that interacts with PKCβII. In vitro studies revealed that GLS1 may be phosphorylated by PKCβII. GLS1 converts glutamine to glutamate, thus the effect of I/R on activity of GLS1 and level of glutamine and glutamate in mitochondria-enriched fraction were measured. RESULTS: Glutaminase activity is higher in CA2‑4 and DG as compared to CA1 in control and 1 h after I/R, and is confirmed by a reduced level of glutamine in this region. Glutamate level seems to be similar in both regions and is not affected by I/R injury. Application of a selective PKCβII inhibitor increased GLS1 activity in both regions. CONCLUSIONS: This indicates that GAC is not relevant in PKCβII‑mediated neuroprotection, however PKCβII seems to have an influence on the maintenance of glutaminase activity. Moreover, we speculate that ischemia‑resistance of CA2‑4 and the DG is due to its high glutaminase activity, which provides a large amount of glutamate that, in turn, can be effectively used for ATP production in the Krebs cycle or for antioxidant defense based on glutathione synthesis. FINANCIAL SUPPORT: This work was supported by National Science Centre grant 2014/15/D/NZ3/02784.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2019
• Tom: 79
• Numer: Suppl.1
• Opis fizyczny: p.LXII

Twórcy

autor

Bochomulski P.

• Molecular Biology Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Krupska O.

• Molecular Biology Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Klimczak P.

• Molecular Biology Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Hilgier W.

• Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Zablocka B.

• Molecular Biology Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Beresewicz M.

• Molecular Biology Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland