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The massive solubility changes of neuronal proteins upon simulated traumatic brain injury

ABSTRACT: The molecular consequences of traumatic brain injuries or TBI are poorly understood. Here, we simulated TBI using an innovative laboratory apparatus employing a 5.1 kg dummy impact generating a ≤3,300 g-force acceleration and performed system-wide profiling of neuronal cells using Proteome Integral Solubility Alteration (PISA) assay. Dynamic impact led to both reduction in neuron viability and massive solubility changes in the proteome. The affected proteins mapped not only to the expected pathways like cell adhesion, collagen and laminin structures, as well as response to stress, but also to other dense protein networks, such as immune response, complement and coagulation cascades. An energy absorbing material largely rescues the loss of cell viability and dampens proteome solubility changes. The cellular effects are found to be mainly due to the shockwave rather than the g-force acceleration. This study paves the way to introducing a proteome-based shock-meter as well as identifying TBI protein biomarkers and potential drug targets for primary prevention and intervention.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Amir Ata Saei

LAB HEAD: Prof. Roman A. Zubarev

PROVIDER: PXD038607 | Pride | 2023-09-23

REPOSITORIES: Pride

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	Centrifuge_g_PISA_Rep01_Frac01.raw	Raw
	Centrifuge_g_PISA_Rep01_Frac02.raw	Raw
	Centrifuge_g_PISA_Rep01_Frac03.raw	Raw
	Centrifuge_g_PISA_Rep01_Frac04.raw	Raw
	Centrifuge_g_PISA_Rep01_Frac05.raw	Raw

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The massive solubility changes of neuronal proteins upon simulated traumatic brain injury

Project description:The molecular consequences of traumatic brain injuries or TBI are poorly understood. Here, we simulated TBI using an innovative laboratory apparatus employing a 5.1 kg dummy impact generating a ≤3,300 g-force acceleration and performed system-wide profiling of neuronal cells using Proteome Integral Solubility Alteration (PISA) assay. Dynamic impact leads to both reduction in neuron viability and massive solubility changes in the proteome. The affected proteins map not only to pathways such as cell adhesion, collagen and laminin structures, as well as response to stress, but also to other dense protein networks, such as immune response, complement and coagulation cascades. An energy absorbing material largely rescues the loss of cell viability and dampens proteome solubility changes. The cellular effects are found to be mainly due to the shockwave rather than the g-force acceleration. This study paves the way to introducing a proteome-based shock-meter as well as identifying TBI protein biomarkers and potential drug targets for prevention and intervention.

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