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The protein PprI provides protection against radiation injury in human and mouse cells.

ABSTRACT: Severe acute radiation injuries are both very lethal and exceptionally difficult to treat. Though the radioresistant bacterium D. radiodurans was first characterized in 1956, genes and proteins key to its radioprotection have not yet to be applied in radiation injury therapy for humans. In this work, we express the D. radiodurans protein PprI in Pichia pastoris yeast cells transfected with the designed vector plasmid pHBM905A-pprI. We then treat human umbilical endothelial vein cells and BALB/c mouse cells with the yeast-derived PprI and elucidate the radioprotective effects the protein provides upon gamma irradiation. We see that PprI significantly increases the survival rate, antioxidant viability, and DNA-repair capacity in irradiated cells and decreases concomitant apoptosis rates and counts of damage-indicative ?H2AX foci. Furthermore, we find that PprI reduces mortality and enhances bone marrow cell clone formation and white blood cell and platelet counts in irradiated mice. PprI also seems to alleviate pathological injuries to multiple organs and improve antioxidant viability in some tissues. Our results thus suggest that PprI has crucial radioprotective effects on irradiated human and mouse cells.

SUBMITTER: Shi Y

PROVIDER: S-EPMC4879577 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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The protein PprI provides protection against radiation injury in human and mouse cells.

Shi Yi Y Wu Wei W Qiao Huiping H Yue Ling L Ren Lili L Zhang Shuyu S Yang Wei W Yang Zhanshan Z

Scientific reports 20160525

Severe acute radiation injuries are both very lethal and exceptionally difficult to treat. Though the radioresistant bacterium D. radiodurans was first characterized in 1956, genes and proteins key to its radioprotection have not yet to be applied in radiation injury therapy for humans. In this work, we express the D. radiodurans protein PprI in Pichia pastoris yeast cells transfected with the designed vector plasmid pHBM905A-pprI. We then treat human umbilical endothelial vein cells and BALB/c ...[more]

PMID: 27222438

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Project description:BACKGROUND: Purified intravenous immunoglobulin (IVIG) obtained from the plasma of healthy humans is indicated for the treatment of primary immunodeficiency disorders associated with defects in humoral immunity. IVIG contains naturally occurring auto-antibodies, including antibodies (Abs) against ?-amyloid (A?) peptides accumulating in the brains of Alzheimer's disease (AD) patients. IVIG has been shown to alleviate AD pathology when studied with mildly affected AD patients. Although its mechanisms-of-action have been broadly studied, it remains unresolved how IVIG affects the removal of natively formed brain A? deposits by primary astrocytes and microglia, two major cell types involved in the neuroinflammatory responses. METHODS: We first determined the effect of IVIG on A? toxicity in primary neuronal cell culture. The mechanisms-of-action of IVIG in reduction of A? burden was analyzed with ex vivo assay. We studied whether IVIG solubilizes natively formed A? deposits from brain sections of APP/PS1 mice or promotes A? removal by primary glial cells. We determined the role of lysosomal degradation pathway and A? Abs in the IVIG-promoted reduction of A?. Finally, we studied the penetration of IVIG into the brain parenchyma and interaction with brain deposits of human A? in a mouse model of AD in vivo. RESULTS: IVIG was protective against A? toxicity in a primary mouse hippocampal neuron culture. IVIG modestly inhibited the fibrillization of synthetic A?1-42 but did not solubilize natively formed brain A? deposits ex vivo. IVIG enhanced microglia-mediated A? clearance ex vivo, with a mechanism linked to A? Abs and lysosomal degradation. The IVIG-enhanced A? clearance appears specific for microglia since IVIG did not affect A? clearance by astrocytes. The cellular mechanisms of A? clearance we observed have potential relevance in vivo since after peripheral administration IVIG penetrated to mouse brain tissue reaching highest concentrations in the hippocampus and bound selectively to A? deposits in co-localization with microglia. CONCLUSIONS: Our results demonstrate that IVIG promotes recognition and removal of natively formed brain A? deposits by primary microglia involving natural A? Abs in IVIG. These findings may have therapeutic relevance in vivo as IVIG penetrates through the blood-brain barrier and specifically binds to A? deposits in brain parenchyma.

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The protein PprI provides protection against radiation injury in human and mouse cells.

Publications

The protein PprI provides protection against radiation injury in human and mouse cells.

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