Cross-Talk in Nucleotide Signaling in Glioma C6 Cells

Wypych, Dorota; Barańska, Jolanta

doi:10.1007/978-3-030-30651-9_3

Dorota Wypych⁶ &
Jolanta Barańska⁶

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1202))

1831 Accesses
4 Citations

Abstract

The chapter is focused on the mechanism of action of metabotropic P2Y nucleotide receptors: P2Y₁, P2Y₂, P2Y₁₂, P2Y₁₄ and the ionotropic P2X₇ receptor in glioma C6 cells. P2Y₁ and P2Y₁₂ both respond to ADP, but while P2Y₁ links to PLC and elevates cytosolic Ca²⁺ concentration, P2Y₁₂ negatively couples to adenylate cyclase, maintaining cAMP at low level. In glioma C6, these two P2Y receptors modulate activities of ERK1/2 and PI3K/Akt signaling and the effects depend on physiological conditions of the cells. During prolonged serum deprivation, cell growth is arrested, the expression of the P2Y₁ receptor strongly decreases and P2Y₁₂ becomes a major player responsible for ADP-evoked signal transduction. The P2Y₁₂ receptor activates ERK1/2 kinase phosphorylation (a known cell proliferation regulator) and stimulates Akt activity, contributing to glioma invasiveness. In contrast, P2Y₁ has an inhibitory effect on Akt pathway signaling. Furthermore, the P2X₇ receptor, often responsible for apoptotic fate, is not involved in Ca²⁺elevation in C6 cells. The shift in nucleotide receptor expression from P2Y₁ to P2Y₁₂ during serum withdrawal, the cross talk between both receptors and the lack of P2X₇ activity shows the precise self-regulating mechanism, enhancing survival and preserving the neoplastic features of C6 cells.

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Abbreviations

Akt:: protein kinase B/Akt kinase
Ap₄A:: p¹,p⁴-Di(adenosine-5′)tetraphosphate
BzATP:: 2’,3′- 0-(4-benzoylbenzoyl)-ATP
[Ca²⁺]_i :: intracellular calcium concentration
DAG:: diacylglycerol
ER:: endoplasmic reticulum
ERK1/2:: extracellular signal-regulated kinases 1/2.
Gap1:: GTP-ase activating protein 1
GBM:: glioblastoma multiforme
GEF:: guanine nucleotide exchange factor
GFAP:: glial fibrillary acidic protein
GFP:: green fluorescent protein
GPCRG:: protein-coupled receptor
IP₃ :: inositol-1,4,5-trisphosphate
LPS:: lipopolysacharide
MEK:: MAP kinase-ERK kinase
2MeSADP:: 2-methylthio ADP
OxATP:: periodate-oxidized ATP
PDK1:: phosphoinositide-dependent protein kinase 1.
PI3K:: phosphatidylinositol 3-kinase
PIP₂ :: phosphatidylinositol-4,5-bisphosphate
PKA:: protein kinase A
PKC:: protein kinase C
PLC:: phospholipase C
PPADS:: pyridoxal-phosphate-6-azophenyl-2^′,4^’disulfonic acid
PTEN:: phosphatase and tensin homolog
PTX:: pertussis toxin
RTK:: receptor tyrosine kinase

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Dorota Wypych & Jolanta Barańska

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Wypych, D., Barańska, J. (2020). Cross-Talk in Nucleotide Signaling in Glioma C6 Cells. In: Barańska, J. (eds) Glioma Signaling. Advances in Experimental Medicine and Biology, vol 1202. Springer, Cham. https://doi.org/10.1007/978-3-030-30651-9_3

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