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Synthesis of plasma proteins in fetal, adult, and neoplastic human brain tissue
Abstract:
The synthesis of plasma proteins directed by mRNA from human brain tissues was studied by combining in vitro or in ovo translation of mRNAs with crossed immunoelectrophoresis of the mRNA-directed labeled polypeptides, followed by autoradiography of the washed plates. Poly(A)-containing mRNA was prepared from different developmental stages of fetal and postnatal human brain and also from primary glioblastomas and meningiomas. Several plasma protein-like polypeptides were identified in the autoradiographs by their migration coordinates in the two-dimensional gels, compared with immunoprecipitates formed by mature, unlabeled, stainable proteins. These included polypeptides migrating like Gc globulin, haptoglobin, fibrinogen, alpha-fetoprotein, transferrin, cholinesterase, and alpha 2-macroglobulin; other, yet unidentified plasma proteins, were also observed. In general, the synthesis of these plasma proteins appeared to be more pronounced in fetal and neoplastic brain tissues than in postnatal tissues. However, clear immunoprecipitates for some of these plasma proteins could also be detected in products directed by mRNA from particular regions of mature, normal brains, indicating that some synthesis of plasma proteins takes place in the human brain even as late as 40 years of age. mRNAs for several proteins were also identified in samples of neoplastic brain. mRNA for transferrin was identified in normal fetal and adult brain but not in either the glioblastomas or meningiomas studied. Microinjected Xenopus oocytes, in which post-translational processing occurs as well, were also used to translate fetal brain mRNA. Several plasma proteins could be detected in the translation products which were induced and stored in the oocytes. These included hemopexin, which could not be detected in the in vitro system. Others, such as cholinesterase, were found to be secreted by the oocytes. These findings indicate that different cell types in the human brain may produce and either store or secrete particular plasma proteins at defined stages in their development.
Insights
Human brain cells can synthesize plasma proteins, particularly during fetal development and in tumors. Some synthesis occurs even in adult brains, with specific proteins like transferrin not found in brain tumors.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- The human brain's capacity to synthesize plasma proteins is not fully understood.
- Plasma proteins are crucial for various physiological functions.
- Investigating brain-specific protein synthesis can reveal novel biological roles.
Purpose of the Study:
- To identify plasma proteins synthesized by human brain tissues.
- To compare plasma protein synthesis across different developmental stages and in brain tumors.
- To explore the cellular localization and secretion of these proteins.
Main Methods:
- In vitro and in ovo translation of messenger RNA (mRNA) from human brain tissues.
- Crossed immunoelectrophoresis and autoradiography to detect synthesized polypeptides.
- Microinjection of mRNA into Xenopus oocytes for post-translational processing analysis.
Main Results:
- Identified synthesis of several plasma protein-like polypeptides, including Gc globulin, haptoglobin, fibrinogen, alpha-fetoprotein, transferrin, cholinesterase, and alpha 2-macroglobulin.
- Plasma protein synthesis was more pronounced in fetal and neoplastic brain tissues compared to postnatal tissues.
- Transferrin mRNA was found in normal brain but absent in studied glioblastomas and meningiomas.
- Xenopus oocytes translated fetal brain mRNA to produce hemopexin and secrete cholinesterase.
Conclusions:
- The human brain synthesizes various plasma proteins, with increased activity during fetal development and in neoplastic conditions.
- Specific cell types in the brain produce and store or secrete plasma proteins at distinct developmental stages.
- The absence of transferrin synthesis in certain brain tumors suggests potential diagnostic or functional implications.