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PubMed:29593095 JSONTXT

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GlyCosmos6-Glycan-Motif-Image

Id Subject Object Predicate Lexical cue image
T1 1201-1208 Glycan_Motif denotes glucose https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G15021LG
T2 1273-1280 Glycan_Motif denotes glucose https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G15021LG

GlyCosmos6-Glycan-Motif-Structure

Id Subject Object Predicate Lexical cue
T1 1201-1208 https://glytoucan.org/Structures/Glycans/G15021LG denotes glucose
T2 1273-1280 https://glytoucan.org/Structures/Glycans/G15021LG denotes glucose

sentences

Id Subject Object Predicate Lexical cue
T1 0-142 Sentence denotes Loss-of-function PCSK9 mutants evade the unfolded protein response sensor GRP78 and fail to induce endoplasmic reticulum stress when retained.
T2 143-315 Sentence denotes The proprotein convertase subtilisin/kexin type-9 (PCSK9) plays a central role in cardiovascular disease (CVD) by degrading hepatic low-density lipoprotein receptor (LDLR).
T3 316-478 Sentence denotes As such, loss-of-function (LOF) PCSK9 variants that fail to exit the endoplasmic reticulum (ER) increase hepatic LDLR levels and lower the risk of developing CVD.
T4 479-593 Sentence denotes The retention of misfolded protein in the ER can cause ER stress and activate the unfolded protein response (UPR).
T5 594-738 Sentence denotes In this study, we investigated whether a variety of LOF PCSK9 variants that are retained in the ER can cause ER stress and hepatic cytotoxicity.
T6 739-881 Sentence denotes Although overexpression of these PCSK9 variants caused an accumulation in the ER of hepatocytes, UPR activation or apoptosis was not observed.
T7 882-979 Sentence denotes Furthermore, ER retention of endogenous PCSK9 via splice switching also failed to induce the UPR.
T8 980-1098 Sentence denotes Consistent with these in vitro studies, overexpression of PCSK9 in the livers of mice had no impact on UPR activation.
T9 1099-1339 Sentence denotes To elucidate the cellular mechanism to explain these surprising findings, we observed that the 94-kDa glucose-regulated protein (GRP94) sequesters PCSK9 away from the 78-kDa glucose-regulated protein (GRP78), the major activator of the UPR.
T10 1340-1535 Sentence denotes As a result, GRP94 knockdown increased the stability of GRP78-PCSK9 complex and resulted in UPR activation following overexpression of ER-retained PCSK9 variants relative to WT secreted controls.
T11 1536-1803 Sentence denotes Given that overexpression of these LOF PCSK9 variants does not cause UPR activation under normal homeostatic conditions, therapeutic strategies aimed at blocking the autocatalytic cleavage of PCSK9 in the ER represent a viable strategy for reducing circulating PCSK9.

Glycosmos6-MAT

Id Subject Object Predicate Lexical cue
T1 1051-1057 http://purl.obolibrary.org/obo/MAT_0000097 denotes livers

kaiyin_test

Id Subject Object Predicate Lexical cue
T1 194-199 Var denotes PCSK9
T2 225-247 Disease denotes cardiovascular disease
T3 257-266 NegReg denotes degrading
T4 267-307 MPA denotes hepatic low-density lipoprotein receptor
T7 325-341 NegReg denotes loss-of-function
T6 348-353 Gene denotes PCSK9
T5 354-362 Var denotes variants
T9 412-420 PosReg denotes increase
T10 421-440 MPA denotes hepatic LDLR levels
T11 445-450 NegReg denotes lower
T12 455-477 MPA denotes risk of developing CVD
T15 748-762 PosReg denotes overexpression
T13 772-777 Gene denotes PCSK9
T14 778-786 Var denotes variants
T16 797-809 PosReg denotes accumulation
T17 817-834 MPA denotes ER of hepatocytes
R1 T1 T3 CauseOf PCSK9,degrading
R10 T13 T14 ThemeOf PCSK9,variants
R11 T14 T16 CauseOf variants,accumulation
R12 T17 T16 ThemeOf ER of hepatocytes,accumulation
R13 T15 T14 ThemeOf overexpression,variants
R2 T4 T3 ThemeOf hepatic low-density lipoprotein receptor,degrading
R3 T2 T4 ThemeOf cardiovascular disease,hepatic low-density lipoprotein receptor
R4 T6 T5 ThemeOf PCSK9,variants
R5 T5 T7 CauseOf variants,loss-of-function
R6 T5 T9 CauseOf variants,increase
R7 T10 T9 ThemeOf hepatic LDLR levels,increase
R8 T5 T11 CauseOf variants,lower
R9 T12 T11 ThemeOf risk of developing CVD,lower

name_no

Id Subject Object Predicate Lexical cue
T1 194-199 Var denotes PCSK9
T2 225-247 Disease denotes cardiovascular disease
T3 257-266 NegReg denotes degrading
T4 267-307 MPA denotes hepatic low-density lipoprotein receptor
T7 325-341 NegReg denotes loss-of-function
T6 348-353 Gene denotes PCSK9
T5 354-362 Var denotes variants
T9 412-420 PosReg denotes increase
T10 421-440 MPA denotes hepatic LDLR levels
T11 445-450 NegReg denotes lower
T12 455-477 MPA denotes risk of developing CVD
T15 748-762 PosReg denotes overexpression
T13 772-777 Gene denotes PCSK9
T14 778-786 Var denotes variants
T16 797-809 PosReg denotes accumulation
T17 817-834 MPA denotes ER of hepatocytes
R1 T1 T3 CauseOf PCSK9,degrading
R10 T13 T14 ThemeOf PCSK9,variants
R11 T14 T16 CauseOf variants,accumulation
R12 T17 T16 ThemeOf ER of hepatocytes,accumulation
R13 T15 T14 ThemeOf overexpression,variants
R2 T4 T3 ThemeOf hepatic low-density lipoprotein receptor,degrading
R3 T2 T4 ThemeOf cardiovascular disease,hepatic low-density lipoprotein receptor
R4 T6 T5 ThemeOf PCSK9,variants
R5 T5 T7 CauseOf variants,loss-of-function
R6 T5 T9 CauseOf variants,increase
R7 T10 T9 ThemeOf hepatic LDLR levels,increase
R8 T5 T11 CauseOf variants,lower
R9 T12 T11 ThemeOf risk of developing CVD,lower

mondo_disease

Id Subject Object Predicate Lexical cue mondo_id
T1 225-253 Disease denotes cardiovascular disease (CVD) http://purl.obolibrary.org/obo/MONDO_0004995

Anatomy-MAT

Id Subject Object Predicate Lexical cue mat_id
T1 1051-1057 Body_part denotes livers http://purl.obolibrary.org/obo/MAT_0000097

HP-phenotype

Id Subject Object Predicate Lexical cue hp_id
T1 225-247 Phenotype denotes cardiovascular disease HP:0001626
T2 249-252 Phenotype denotes CVD HP:0001626
T3 474-477 Phenotype denotes CVD HP:0001626

NCBITAXON

Id Subject Object Predicate Lexical cue db_id
T1 1061-1065 OrganismTaxon denotes mice 10088

Anatomy-UBERON

Id Subject Object Predicate Lexical cue uberon_id
T1 111-120 Body_part denotes reticulum http://purl.obolibrary.org/obo/UBERON_0007361
T2 397-406 Body_part denotes reticulum http://purl.obolibrary.org/obo/UBERON_0007361
T3 823-834 Body_part denotes hepatocytes http://purl.obolibrary.org/obo/CL_0000182

CL-cell

Id Subject Object Predicate Lexical cue cl_id
T1 823-834 Cell denotes hepatocytes http://purl.obolibrary.org/obo/CL:0000182