Dataset Information

Proteomic analysis of secretory granules in dopaminergic neurons of Parkinson`s disease

ABSTRACT: Parkinson disease (PD) is the second most common age-related neurodegenerative disorder, which is related to neurotransmitter secretion impartment and the dysfunction of vesicle transport. Secretory granules (SGs) are a class of intracellular vesicles different from synaptic vesicles (SVs) in neurons and the neuroendocrine cells. They represent the primary subcellular site for the biosynthesis, storage and releasing of the neuropeptides, neurotransmitters and hormones. In the current study, we characterized the proteome of secretory granules in dopaminergic neurons in PD. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was used to identify proteins in SGs. A total of 4249 proteins were identified in the SGs in normal and MPP+-treated SH-Sy5Y dopaminergic neurons in total. This study regarded the biological alternations of SGs in PD as an entry point. By studying the significantly differentially expressed proteins, it is helpful to better understand the molecular mechanisms of SGs disorders in the pathology of PD, and provide a basis for vesicle transport theory in pathogenesis of PD.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Xiaoni ZHan

LAB HEAD: Xiaoni Zhan

PROVIDER: PXD023937 | Pride | 2021-08-26

REPOSITORIES: Pride

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Proteomic characterization of secretory granules in dopaminergic neurons indicates chromogranin/secretogranin-mediated protein processing impairment in Parkinson's disease.

Wen Gehua G Pang Hao H Wu Xu X Jiang Enzhu E Zhang Xique X Zhan Xiaoni X

Aging 20210821 16

Parkinson's disease (PD) is an aging disorder related to vesicle transport dysfunctions and neurotransmitter secretion. Secretory granules (SGs) are large dense-core vesicles for the biosynthesis of neuropeptides and hormones. At present, the involvement of SGs impairment in PD remains unclear. In the current study, we found that the number of SGs in tyrosine hydroxylase-positive neurons and the marker proteins secretogranin III (Scg3) significantly decreased in the substantia nigra and striatum ...[more]

PMID: 34420933

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Project description:The cardinal clinical features of Parkinson's disease (PD) (rigidity, rest tremor, bradykinesia, and postural instability) result from selective loss of midbrain dopaminergic neurons. More specifically, dopaminergic neurons in the substantia nigra pars compacta (SNc) are much more susceptible to damage than the adjacent dopaminergic neurons in the ventral tegmental area (VTA). This dichotomy is not only seen in human Parkinson's disease, but also in many animal models of PD, including administration of the mitochondrial toxin rotenone to rats, which replicates many of the behavioral and neuropathological features of PD. The factors underlying this selective vulnerability are unknown, but could be related to differences in neuronal circuitry, differences in glial support, or intrinsic differences between the neuronal populations of the two regions. Elucidation of these factors may lead to a greater understanding of the pathogenesis and treatment of Parkinson's disease. We will determine gene expression profiles of untreated rat SNc and VTA dopaminergic neurons using laser capture microscopy to obtain region-specific neuronal mRNA. There are intrinsic differences in gene expression between dopaminergic neurons in the rat SNc and VTA that result in greater susceptibility of SNc neurons to degeneration in experimental parkinsonism. These differences may be related to dopamine metabolism, oxidative metabolism and stress, protein aggregation, or other unforseen pathways. We will compare gene expression profiles between SNc and VTA dopaminergic neurons in normal rats. No treatment or time points will be studied in this experiment. Animals will be anesthetized, sacrificed by decapitation, and brains frozen on dry ice. Frozen sections will be collected onto glass microscope slides and rapidly immunostained for tyrosine hydroxylase to identify dopaminergic neurons. SNc and VTA neurons (approx. 200 per sample) will be isolated using laser capture microscopy. Total RNA will be extracted and poly-A RNA will be amplified using a modified Eberwine protocol. aRNA will be sent to the centers for labeling and hybridization to Affymetrix rat U34A arrays. We have confirmed with the center that our aRNA protocol is compatible with the centers amplification protocols; in fact, it is essentially identical. We will be providing a two-round amplification product to the center for labeling and hybridization. We recognize that using RNA after three rounds of amplification may decrease sensitivity for low copy number transcripts, but favor this approach versus pooling our samples (which are inherently paired) at this point. We have discussed this point in detail with the center. SNc and VTA samples from eight animals (16 samples total) will be provided to mitigate differences specific to individual animals. With the assisatnce of the center, paired t-tests will be used to determine differential expression between the two regions. Permutational t-test analysis and/or Benjamini and Hochberg analysis of expression ratios will be used to protect against multiple comparisons. Selected differentially expressed genes will be validated on separate tissue samples using quantitative RT-PCR or in situ hybridization.

			Action	DRS
	SH-SY5Y_Control1.raw	Raw
	SH-SY5Y_Control2.raw	Raw
	SH-SY5Y_Control3.raw	Raw
	SH-SY5Y_MPP_treated1.raw	Raw
	SH-SY5Y_MPP_treated2.raw	Raw