Up-regulation of PSMB4 is associated with neuronal apoptosis after neuroinflammation induced by lipopolysaccharide

Shi, Jianzhong; Liu, Xiaorong; Xu, Changde; Ge, Jingping; Ren, Jianbing; Wang, Jun; Song, Xinjian; Dai, Shirong; Tao, Weidong; Lü, Hongjian

doi:10.1007/s10735-015-9637-0

Cited by 9 publications

(4 citation statements)

References 35 publications

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“…B3GALTL, as mentioned above, is a glycosyltransferase that adds glycans to proteins in glycosylation 41 , and GMPPB, a GDP-mannose pyrophosphorylase B, catalyzes the formation of GDP-mannose, which is required for the glycosylation of lipids and proteins 47 . PSMB4 is a proteasome that is responsible for protein degradation and is involved in neuronal apoptosis in neuroinflammation 48 . Finally, CDH13 encodes a calcium-dependent cell adhesion protein that has been implicated in major depression, bipolar disorder, schizophrenia, ADHD, and autism spectrum disorder 49 .…”

Section: Discussionmentioning

confidence: 99%

Brain proteome-wide association study implicates novel proteins in depression pathogenesis

et al. 2021

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Depression is a common condition but current treatments for depression are only effective in a subset of individuals. To identify novel treatment targets, we integrated depression GWAS results (N=500,199) with human brain proteomes (N=376) to perform a proteome-wide association study (PWAS) of depression, followed by Mendelian randomization. We identified 19 genes consistent with being causal in depression, acting via their cis -regulated brain protein abundance. We replicated 9 of these genes using an independent depression GWAS (N=307,353) and human brain proteomic dataset (N=152). Eleven of these 19 genes also had their cis -regulated mRNA levels associated with depression based on integration of the depression GWAS with human brain transcriptomes (N=888). Meta-analysis of the discovery and replication PWAS identified 25 brain proteins consistent with being causal in depression, and 20 were not previously implicated in depression by GWAS. Together, these findings provide novel promising brain protein targets for further mechanistic and therapeutic studies.

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Section: Discussionmentioning

confidence: 99%

Brain proteome-wide association study implicates novel proteins in depression pathogenesis

et al. 2021

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“…Indeed, the neuroinflammation induced by LPS has been related to ABBREVIATIONS: CT-L, chymotrypsin-like; DG, dentate gyrus; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GCDG, green cell in dentate gyrus; GFAP, glial fibrillary acidic protein; GFP, green fluorescent protein; Iba-1, ionized calcium-binding adapter molecule 1; NeuN, neuronal nuclei; P2Y 2 , P2Y purinoceptor 2; P2Y 2 R, P2Y purinoceptor 2 receptor; P2Y 2 R 2/2 , P2Y purinoceptor 2 receptor deficient; PG-L, postglutamyl-like; Ub G76V -GFP/UbGFP, ubiquitin G76V -green fluorescent protein; Up 4 U, diuridine tetraphosphate; UPS, ubiquitin-proteasome system; WT, wild type alterations in the expression of the 20S catalytic subunits b5 and b5i, as well as in the catalytic proteasomal activity (9)(10)(11). Additionally, the proteasome 20S complex subunit b4 and the 19S complex subunit Rpn9 have been, respectively, involved in the neuronal loss (12) and the production of proinflammatory mediators (13) caused by LPS-induced neuroinflammation. However, which molecular mechanisms underlying the proteasomal alterations are produced by the LPS-induced neuroinflammation, as well as which neural lineages are more susceptible to these changes, are still unresolved questions.…”

mentioning

confidence: 99%

“…Indeed, the neuroinflammation induced by LPS has been related to alterations in the expression of the 20S catalytic subunits b5 and b5i, as well as in the catalytic proteasomal activity (9)(10)(11). Additionally, the proteasome 20S complex subunit b4 and the 19S complex subunit Rpn9 have been, respectively, involved in the neuronal loss (12) and the production of proinflammatory mediators (13) caused by LPS-induced neuroinflammation. However, which molecular mechanisms underlying the proteasomal alterations are produced by the LPS-induced neuroinflammation, as well as which neural lineages are more susceptible to these changes, are still unresolved questions.…”

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confidence: 99%

The regulation of proteostasis in glial cells by nucleotide receptors is key in acute neuroinflammation

et al. 2018

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The disturbances of cellular proteostasis caused by the alteration in the ubiquitin-proteasome system (UPS) have been proposed as a common mechanism underlying several neural pathologies that involve a neuroinflammatory process. As we have previously reported that the nucleotide receptor P2Y purinoceptor 2 (P2YR) regulates the proteasomal catalytic activities, we wonder whether this receptor is involved in the UPS disturbances associated with the neuroinflammation process. With the use of mice expressing a UPS reporter [mice expressing the UPS reporter ubiquitin-green fluorescent protein (UbGFP mice)], we found that LPS-induced acute neuroinflammation status causes a UPS impairment in astrocytes and microglial cells by a mechanism dependent on P2YR. In this line, LPS-treated double transgenic UbGFP; P2YR mice did not present a UPS impairment in astrocytes or a social interaction deficit as severe as that observed in LPS-treated UbGFP mice. In vivo administration of selective P2YR agonist diuridine tetraphosphate reversed the UPS impairment completely in astrocytes and partially in microglial cells, promoting increased expression of the proteasomal β5 subunit by a mechanism dependent on the Src/PI3K/ERK pathway. Altogether, our results suggest that LPS induces unbalanced proteostasis in astrocytes by blocking P2YR. Finally, our findings point to the design of selective P2YR agonist drugs as a new therapeutic approach to treat the neuroinflammatory status.-De Diego García, L., Sebastián-Serrano, Á., Hernández, I. H., Pintor, J., Lucas, J. J., Díaz-Hernández, M. The regulation of proteostasis in glial cells by nucleotide receptors is key in acute neuroinflammation.

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“…PSMB4 is a β subunit of the 20S core proteasome ( , accessed on 6 September 2022). Though the biochemical functions of PSMB4 remain obscure, its involvement in several tumors and neuronal dysfunction has been documented [ 20 , 29 , 30 , 31 , 32 , 33 ]. Hepatitis B virus (HBV) X protein (HBx) was involved in the development of HBV-related hepatocellular carcinoma (HCC).…”

Section: Discussionmentioning

confidence: 99%

Cellular PSMB4 Protein Suppresses Influenza A Virus Replication through Targeting NS1 Protein

Yang

Hsu

Lai

et al. 2022

Viruses

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The nonstructural protein 1 (NS1) of influenza A virus (IAV) possesses multiple functions, such as the inhibition of the host antiviral immune responses, to facilitate viral infection. To search for cellular proteins interacting with the IAV NS1 protein, the yeast two-hybrid system was adopted. Proteasome family member PSMB4 (proteasome subunit beta type 4) was found to interact with the NS1 protein in this screening experiment. The binding domains of these two proteins were also determined using this system. The physical interactions between the NS1 and cellular PSMB4 proteins were further confirmed by co-immunoprecipitation assay and confocal microscopy in mammalian cells. Neither transiently nor stably expressed NS1 protein affected the PSMB4 expression in cells. In contrast, PSMB4 reduced the NS1 protein expression level, especially in the presence of MG132. As expected, the functions of the NS1 protein, such as inhibition of interferon activity and enhancement of transient gene expression, were suppressed by PSMB4. PSMB4 knockdown enhances IAV replication, while its overexpression attenuates IAV replication. Thus, the results of this study suggest that the cellular PSMB4 protein interacts with and possibly facilitates the degradation of the NS1 protein, which in turn suppresses IAV replication.

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Up-regulation of PSMB4 is associated with neuronal apoptosis after neuroinflammation induced by lipopolysaccharide

Cited by 9 publications

References 35 publications

Brain proteome-wide association study implicates novel proteins in depression pathogenesis

Brain proteome-wide association study implicates novel proteins in depression pathogenesis

The regulation of proteostasis in glial cells by nucleotide receptors is key in acute neuroinflammation

Cellular PSMB4 Protein Suppresses Influenza A Virus Replication through Targeting NS1 Protein

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