Purinergic P2Y2 receptors promote hepatocyte resistance to hypoxia

Carini, Rita; Alchera, Elisa; Cesaris, Maria Grazia De; Splendore, Roberta; Piranda, Daniela; Baldanzi, Gianluca; Albano, Emanuele

doi:10.1016/j.jhep.2006.02.017

Cited by 21 publications

(28 citation statements)

References 40 publications

(76 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Each of these receptors can increase intracellular Ca [30], bile secretion [25] and liver regeneration [31]. Results were confirmed in at least three independent experiments.…”

Section: Functionality Of P2x Receptors In Hepatocytessupporting

confidence: 54%

Rat hepatocytes express functional P2X receptors

et al. 2007

View full text Add to dashboard Cite

Extracellular ATP regulates many hepatic functions by stimulating purinergic receptors. Only the G protein‐coupled P2Y receptors have been studied in hepatocytes. We investigated the functional expression of P2X receptors, the ATP‐gated channels in rat hepatocytes. P2X4 and P2X7 transcripts and proteins were detected by RT‐PCR and by both Western blotting and immunocytochemistry. High concentrations of ATP, and 2′‐and 3′‐O‐(4‐benzoylbenzoyl)‐ATP the preferring agonist of P2X7, induced membrane blebbing and significant uptake of 4‐[(3‐methyl‐2(3H)‐benzoxazolylidene)methyl]‐1‐[3‐(triethylammonio)propyl]diiodide, both of which were inhibited by oxidised ATP, a blocker of P2X receptors. These results provide evidence that P2X4 and P2X7 receptors are expressed and functional on rat hepatocytes, possibly playing an important role in the purinergic signaling complex in these cells.

show abstract

“…Each of these receptors can increase intracellular Ca [30], bile secretion [25] and liver regeneration [31]. Results were confirmed in at least three independent experiments.…”

Section: Functionality Of P2x Receptors In Hepatocytessupporting

confidence: 54%

Rat hepatocytes express functional P2X receptors

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Targeting this pathway may be of interest beyond PKD. For instance, P2Y2R has been reported to play a role in acute ischemic heart injury [37] and hypoxic liver injury [38].…”

Section: Discussionmentioning

confidence: 99%

P2Y2R is a direct target of HIF-1α and mediates secretion-dependent cyst growth of renal cyst-forming epithelial cells

Kraus

Grampp

Goppelt‐Struebe

et al. 2016

Purinergic Signalling

View full text Add to dashboard Cite

Polycystic kidney diseases are characterized by numerous renal cysts that continuously enlarge resulting in compression of intact nephrons and tissue hypoxia. Recently, we have shown that hypoxia-inducible factor (HIF)-1α promotes secretion-dependent cyst expansion, presumably by transcriptional regulation of proteins that are involved in calciumactivated chloride secretion. Here, we report that HIF-1α directly activates expression of the purinergic receptor P2Y2R in human primary renal tubular cells. In addition, we found that P2Y2R is highly expressed in cyst-lining cells of human ADPKD kidneys as well as PKD1 orthologous mouse kidneys. Knockdown of P2Y2R in renal collecting duct cells inhibited calcium-dependent chloride secretion in Ussing chamber analyses. In line with these findings, knockdown of P2Y2R retarded cyst expansion in vitro and prevented ATPand HIF-1α-dependent cyst growth. In conclusion, P2Y2R mediates ATP-dependent cyst growth and is transcriptionally regulated by HIF-1α. These findings provide further mechanistic evidence on how hypoxia promotes cyst growth.

show abstract

“…1B). Although previous studies have shown that strychnine, a specific antagonist of glycine receptors, interfered with glycine signaling in both hepatocytes and Kupffer cells [6,19], the addition of strychnine (10 lmol/L) before hepatocyte incubation with glycine did not affect p38 MAPK phosphorylation and the tolerance to hypoxia (Figs. 1A and B).…”

Section: Role Of P38 Mapk In Glycine-induced Protectionmentioning

confidence: 75%

“…Cytosolic pH and pH recovery were measured using the fluorescent indicator dye 2 0 ,7 0 -bis(carboxyethyl)-5,6-carboxyfluorescein-acetoxymethyl ester (BCECF-AM) (Molecular Probes, Eugene, OR, USA) as previously described [19].…”

Section: Measurement Of Cytosolic Phmentioning

confidence: 99%