Evidence mapPaperPMID 40202072Full record

ArticleCNS neuroscience & therapeutics2025

Phosphorylation of cAMP-Activated Exchange Protein-1 Participates in Neuroprotection and Ferroptosis Regulation Following Intracerebral Hemorrhage in Rats.

Guannan Jiang, Jialei Zhou, Yan Zhuang, Siyuan Yang, Gang Chen, Wanchun You, Xiang Li

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Article in CNS neuroscience & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

7 authors.

Guannan JiangDepartment of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China.
Jialei ZhouDepartment of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China.
Yan ZhuangDepartment of Neurosurgery, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Siyuan YangDepartment of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China.
Gang ChenDepartment of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China.
Wanchun YouDepartment of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China.
Xiang LiDepartment of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China.ORCID 0000-0002-9918-5847

Funding

the National Natural Science Foundation of China 82471334the Natural Science Foundation of Jiangsu Province BK20220096
6 · The paper itself

Abstract

backgroundIntracerebral hemorrhage (ICH) is a severe condition characterized by elevated mortality and disability rates. The cAMP-activated exchange protein-1 (EPAC-1) is implicated in various cytoprotective mechanisms; however, its specific role in ICH remains unclear.

methodsA rat model of ICH was established by injecting autologous blood, while the in vitro primary neuronal model was stimulated using oxyhemoglobin (OxyHb). The construction of EPAC-1 overexpression wild-type (WT) and phosphorylated mutant plasmids (S108A or S108E), as well as lentiviruses, was performed for in vitro and in vivo studies.

resultsThe cAMP signaling pathway was found to be significantly enriched following ICH by high-throughput sequencing analysis. Our findings showed that while EPAC-1 protein levels remained relatively unchanged after ICH, RabGEF activity was conspicuously upregulated. This was accompanied by a marked decrease in EPAC-1 phosphorylation levels. Mutations that activate EPAC-1 phosphorylation led to significant improvements in neuronal survival and behavioral outcomes after ICH. Bioinformatics analysis revealed that ferroptosis was significantly enriched after ICH and showed a positive correlation with EPAC-1 serine phosphorylation. EPAC-1 phosphorylation activating mutations inhibit neuronal ferroptosis, whereas inactivating mutations exacerbate it.

conclusionThe phosphorylation of EPAC-1 is essential for maintaining neuronal survival, which may be related to ferroptosis inhibition after ICH.

Indexed as

Cerebral HemorrhageFerroptosisGuanine Nucleotide Exchange FactorsNeuroprotectionAnimalsMaleNeuronsPhosphorylationRatsRats, Sprague-DawleyGuanine Nucleotide Exchange FactorsRapgef3 protein, ratcAMP‐activated exchange protein‐1ferroptosisintracerebral hemorrhageneuroprotectionphosphorylation

Identifiers

PMID40202072
PMCPMC11979711

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.