Adenosine uptake is the major effector of extracellular ATP toxicity in human cervical cancer cells.
Bottom Line: Corroborating these data, blockage or knockdown of P2 × 7 only slightly reduced ATP cytotoxicity.Moreover, ATP-induced apoptosis and signaling-p53 increase, AMPK activation, and PARP cleavage-as well as autophagy induction were also inhibited by dipyridamole.In addition, inhibition of adenosine conversion into AMP also blocked cell death, indicating that metabolization of intracellular adenosine originating from extracellular ATP is responsible for the main effects of the latter in human cervical cancer cells.
Affiliation: Laboratory of Biochemical and Cytological Analysis, Faculty of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil.Show MeSH
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Mentions: Extracellular ATP increased the levels of pAMPK(T172)—the active state of AMPK (Hardie et al., 2006)—in a time-dependent manner, mainly after 48 and 72 h, accompanied by PARP cleavage (Figure 7A). p53 levels reached the highest levels at 48 h and these molecular alterations were suppressed almost completely by DIP pretreatment. Furthermore, DIP pretreatment increased the levels of Bcl2, a classical antiapoptotic protein, after 72 h of ATP treatment. Taken together, these data suggest that adenosine uptake is responsible for the main molecular alterations that underlie the toxicity of extracellular ATP in cervical cancer cells.
Affiliation: Laboratory of Biochemical and Cytological Analysis, Faculty of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil.