Ecto-F₀/F₁ ATPase as a novel candidate of prothymosin α receptor

Abstract

The present study suggests that ProTα may activate ecto-F/F ATPase and produced ATP. This study leads to next subjects whether produced ATP and its metabolites, ADP or adenosine may activate corresponding G-coupled receptors.

Prothymosin alpha and its mimetic hexapeptide improve delayed tissue plasminogen activator‐induced brain damage following cerebral ischemia

“…In PIT ischemia model, P6Q treatment with tPA upto 6 h also inhibited brain damage without hemorrhage and motor dysfunction evaluated by Rotarod test. The next important goal will be to clarify the molecular-and cellular-based mechanisms underlying ProTa-or P6Qinduced beneficial effects against the cellular damage using a combination of ischemia/reperfusion and tPA using CLARITY system in the brain and vascular cell culture system, as we recently reported two candidate receptors for ProTa, which are TLR4 and plasma F0/F1 ATPase in the plasma membrane (Halder et al 2015;Ueda et al 2018). As the beneficial effects of ProTa/P6Q are apparent despite the small sample size, future experiments will be performed using additional number of animals and a more detailed histological analysis to permit a more thorough analysis of different parameters, including dose optimization and therapeutic window.…”

“…ProTa activates toll-like receptor 4 (TLR4) and its downstream TIR-domain-containing adapter-inducing interferon-b (TRIF) signaling to prevent the ischemic retina (Halder et al 2015). Recently, we reported that ProTa activates G i -coupled receptor ecto-F 0 /F 1 ATPase and produces ATP in HUVECs culture (Ueda et al 2018). We previously showed the protective effects of ProTa-derived 30-amino acid (a.a. 49-78) or 9-amino acid (a.a. 52-60) peptide in retinal and cerebral ischemia or serum-starvation stress (Halder et al 2013a;Halder et al 2013b).…”