Type

Journal Article

Authors

Eva M Jimenez-Mateos
David C Henshall
Orla Watters
Edward Beamer
Mariana Alves
Amaya Sanz-Rodriguez
Gary P Brennan
Tobias Engel

Subjects

Biochemistry

Topics
feed forward 1 protein microrna expression status epilepticus protein expression transcription factors purinergic receptor sp1 transcription factor

A calcium-sensitive feed-forward loop regulating the expression of the ATP-gated purinergic P2X7 receptor via specificity protein 1 and microRNA-22. (2016)

Abstract Cells have developed complex transcriptional regulatory mechanisms to maintain intracellular homeostasis and withstand pathophysiological stressors. Feed-forward loops comprising transcription factors that drive expression of both target gene and a microRNA as negative regulator, are gaining increasing recognition as key regulatory elements of cellular homeostasis. The ATP-gated purinergic P2X7 receptor (P2X7R) is an important driver of inflammation and has been implicated in the pathogenesis of numerous brain diseases including epilepsy. Changes in P2X7R expression have been reported in both experimental models and in epilepsy patients but the mechanism(s) controlling P2X7R levels remain incompletely understood. The specificity protein 1 (Sp1) has been shown to induce P2X7R transcription in vitro and recent data has identified microRNA-22 as a post-transcriptional repressor of P2X7R expression after seizures. In the present study we show that Sp1 can induce the transcription of both microRNA-22 and P2X7R in vitro during increased neuronal activity and in vivo in a mouse model of status epilepticus. We further show that Sp1-driven microRNA-22 transcription is calcium-sensitive and Sp1 occupancy of the microRNA-22 promoter region is blocked under conditions of seizure activity sufficient to elicit neuronal death. Taken together, our results suggest a neuronal activity-dependent P2X7R expression which is induced by the transcription factor Sp1 and repressed in a calcium-dependent manner by microRNA-22.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Eva M Jimenez-Mateos, David C Henshall, Orla Watters, Edward Beamer, Mariana Alves, Amaya Sanz-Rodriguez, Gary P Brennan, Tobias Engel

Experts in our system

1
Eva M Jimenez-Mateos
Royal College of Surgeons in Ireland
Total Publications: 55
 
2
David C Henshall
Royal College of Surgeons in Ireland
Total Publications: 127
 
3
Orla Watters
Royal College of Surgeons in Ireland
Total Publications: 5
 
4
Edward Beamer
Royal College of Surgeons in Ireland
Total Publications: 3
 
5
Mariana Alves
Royal College of Surgeons in Ireland
Total Publications: 9
 
6
Amaya Sanz-Rodriguez
Royal College of Surgeons in Ireland
Total Publications: 18
 
7
Gary P Brennan
Royal College of Surgeons in Ireland
Total Publications: 14
 
8
Tobias Engel
Royal College of Surgeons in Ireland
Total Publications: 66