Background: Factor XII (FXII) is a serine protease that participates in the intrinsic coagulation pathway. Several studies have shown that plasma FXII exerts a deleterious role in cerebral ischemia and traumatic brain injury by promoting thrombo-inflammation. Nevertheless, the impact of FXII on neuronal cell fate remains unknown.
Objectives: We investigated the role of FXII and FXIIa in neuronal injury and apoptotic cell death.
Methods: We tested the neuroprotective roles of FXII and FXIIa in an experimental model of neuronal injury induced by stereotaxic intracerebral injection of N-methyl-D-aspartic acid (NMDA) in vivo and in a model of apoptotic death of murine primary neuronal cultures through serum deprivation in vitro.
Results: Here, we found that exogenous FXII and FXIIa reduce brain lesions induced by NMDA injection in vivo. Furthermore, FXII protects cultured neurons from apoptosis through a growth factor--like effect. This mechanism was triggered by direct interaction with epidermal growth factor (EGF) receptor and subsequent activation of this receptor. Interestingly, the "proteolytically" active and two-chain form of FXII, FXIIa, exerts its protective effects by an alternative signaling pathway. FXIIa activates the pro-form of hepatocyte growth factor (HGF) into HGF, which in turn activated the HGF receptor (HGFR) pathway.
Conclusion: This study describes two novel mechanisms of action of FXII and identifies neurons as target cells for the protective effects of single and two-chain forms of FXII. Therefore, inhibition of FXII in neurological disorders may have deleterious effects by preventing its beneficial effects on neuronal survival.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1111/jth.15414 | DOI Listing |
Int J Biol Macromol
December 2024
Laboratory of Molecular Medicine, Ordos Central Hospital, Inner Mongolia Autonomous Region, Ordos 017000, China; Ordos Clinical Medical College, Inner Mongolia Medical University, Ordos 017000, China; Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014000, China. Electronic address:
Salivary proteins of ticks can inhibit host hemostatic and inflammatory responses during the blood-sucking process of the parasites. A cDNA sequence, Hq021, was identified from a cDNA library of Haemaphysalis qinghaiensis. Hq021 encodes a mature protein containing 182 amino acids with a molecular mass of 20.
View Article and Find Full Text PDFJ Biol Chem
December 2024
Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR; Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR.
Lipopolysaccharide (LPS) is the primary pathogenic factor in Gram-negative sepsis. While the presence of LPS in the bloodstream during infection is associated with disseminated intravascular coagulation, the mechanistic link between LPS and blood coagulation activation remains ill-defined. The contact pathway of coagulation-a series of biochemical reactions that initiates blood clotting when plasma factors XII (FXII) and XI (FXI), prekallikrein (PK) and high molecular weight kininogen (HK) interact with anionic surfaces-has been shown to be activated in Gram-negative septic patients.
View Article and Find Full Text PDFBlood Res
October 2024
Daisy Hill Hospital, 5 Hospital Road, Newry, BT35 8DR, UK.
The classic coagulation cascade model of intrinsic and extrinsic coagulation pathways, i.e. contact activation pathway and tissue factor pathway, has been widely modified.
View Article and Find Full Text PDFFront Allergy
September 2024
Takeda Development Center Americas Inc., Cambridge, MA, United States.
Nat Commun
September 2024
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!