scholarly journals Human Cord Blood Serum-Derived APP α-Secretase Cleavage Activity is Mediated by C1 Complement

2018 ◽  
Vol 27 (4) ◽  
pp. 666-676 ◽  
Author(s):  
Ahsan Habib ◽  
Darrell Sawmiller ◽  
Huayan Hou ◽  
Manasa Kanithi ◽  
Jun Tian ◽  
...  

Alzheimer’s Disease (AD) is the leading cause of dementia in the elderly. In healthy individuals, amyloid precursor protein (APP) is cleaved by α-secretase, generating soluble α-amyloid precursor protein (sAPPα), which contributes neuroprotective functions in the neuronal environment. In contrast, in the neurodegenerative environment of AD patients, amyloid-β-peptide (Aβ) of either 40 or 42 residues are generated by increased activity of β- and γ-secretase. These proteins amalgamate in specific regions of the brain, which disrupts neuronal functions and leads to cognitive impairment. Human umbilical cord blood cells (HUCBC) have proven useful as potential immunomodulatory therapies in various models of neurodegenerative diseases, including AD. Our most recent work studied the impact of umbilical cord blood serum (CBS) on modulation of sAPPα production. Heat-sensitive CBS significantly promoted sAPPα production, indicating that heat-sensitive factor(s) play(s) a role in this process. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis was used to determine the molecular source of α-secretase in purified CBS and aged blood serum (AgBS) fraction. Of the proteins identified, the subunits of C1 complex (C1q, C1r, and C1s) and alpha-2-macroglobulin showed significantly greater levels in purified α-CBS fraction (α-CBSF) compared with the AgBS fraction (AgBSF). Specifically, C1 markedly increased sAPPα and alpha-carboxyl-terminal fragment (α-CTF) production in a dose-dependent fashion, whereas C1q alone only minimally increased and C3 did not increase sAPPα production in the absence of sera. Furthermore, C1q markedly increased sAPPα and α-CTF, while decreasing Aβ, in CHO/APPwt cells cultured in the presence of whole sera. These results confirm our initial assumption that APP α-secretase activity in human blood serum is mediated by complement C1, opening a potential therapeutic modality for the future of AD.

2020 ◽  
Vol 10 (2) ◽  
pp. 2167-2173

Application of mediators directly to the injured site to promote de novo tissue can be the most promising strategy in regenerative medicine. However, understanding the mechanism of regional application of proteins /growth factors is challenging. Likewise, the proteins from Human Umbilical Cord Blood Serum(hUCBS) remain inadequately understood in terms of its therapeutic use. Several biological processes of the components in hUCBS remains unanswered. Human umbilical cord blood was collected in vacutainer tubes from 35 healthy mothers.hUCBS was obtained after centrifuge -4oC at 10,000 rpm for 20minutes. After the removal of high abundant proteins, proteomic profiling of UCBS was done by Mass Spectrometry. The Mascot search engine was used for peptide sequence identification. Proteins identified were assessed for tissue expression, cellular components, and biological functions based on Gene Ontology (GO) analyses. A total of 99 proteins were detected. The tissue expression information of proteins obtained included the Stomach, Liver, Heart, Lungs. Around 91 proteins were expressed in embryo organs. Proteins in hUBCS reflect the physiological status of the fetus/pregnancy. Major proteins found in hUCBS were expressed in the embryo, indicating that proteins were involved in organ development. Data contributed to a better understanding of the protein functions present in hUCBS.


2007 ◽  
Vol 53 (6) ◽  
pp. 303-307 ◽  
Author(s):  
Z.-G. Zhang ◽  
J.-H. Zhao ◽  
Z.-L. Wei ◽  
L. Cong ◽  
P. Zhou ◽  
...  

2020 ◽  
Vol 2 (2) ◽  
pp. 29-30

A few biomedical applications of Human umbilical cord blood serum used for the treatment of blood disorders and ocular therapy have been documented. Umbilical cords are relatively free of bacterial and viral contamination and often discarded after birth. Previous studies on human umbilical cord blood serum have certain factors exhibiting a distinctive differentiation potential and pharmacological influence like to boost anti-inflammatory, analgesic, and wound healing property. Cord blood can be collected without pain and cryopreserved without causing any changes in the functional properties. Human umbilical cord blood serum has been increasingly used in regenerative medicine because of their ability to treat tissue injury and causing immunomodulatory properties. Human cord blood serum possesses a striking natural resemblance of nutrients required for cell/tissue engineering. Cord blood serum being allogenic in nature, makes it a favorable biomaterial over other autogenous therapies. It contains a number of proteins that are exchanged from the mother to the fetus for growth and development.These exclusive proteins may perhaps participate in the modulation of cell proliferation and differentiation along with accelerated migration of keratinocyte at the wound edge with the generation of the intact epithelium.In the present study, umbilical cord blood serum was obtained from 35 patients and was subjected toMass Spectrometry. A total of 99 proteins were identified in the sample. Functions of proteins were analyzed using the Uniprot database.Thus, understanding the protein functions could give us insight into the regenerative properties of umbilical cord blood serum.


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