General Information:

Id: 11,680
Diseases: Metabolic
Muscular
Mus musculus
ACE2 KO mouse
undifferentiated mouse C2C12 myoblast cells
article/cited
Reference: Cao X et al.(2019) Angiotensin-converting enzyme 2 regulates endoplasmic reticulum stress and mitochondrial function to preserve skeletal muscle lipid metabolism Lipids Health Dis 18: 207 [PMID: 31775868]

Interaction Information:

Comment ACE2 deficiency in vivo displayed lipid accumulation, ER stress and mitochondrial dysfunction in skeletal muscle.
Formal Description
Interaction-ID: 116053

phenotype

ACE2 deficiency

increases_activity of

process

lipid storage

in vivo in mouse skeletal muscle
Comment ACE2 deficiency in vivo displayed lipid accumulation, ER stress and mitochondrial dysfunction in skeletal muscle.
Formal Description
Interaction-ID: 116079

phenotype

ACE2 deficiency

increases_activity of

in vivo in mouse skeletal muscle
Comment Activation of ACE2 can ameliorate ER stress and mitochondrial function, which slightly accompanied by reduced TG content and down-regulated the expression of skeletal muscle lipogenic proteins in the db/db mice.
Formal Description
Interaction-ID: 116080

gene/protein

ACE2

decreases_activity of

decreasing ER stress via activation of ACE2
Drugbank entries Show/Hide entries for ACE2
Comment ACE2 improves skeletal muscle lipid metabolism in vitro and in vivo.
Formal Description
Interaction-ID: 116081

gene/protein

ACE2

increases_activity of

in mouse skeletal muscle in vivo and in vitro
Drugbank entries Show/Hide entries for ACE2
Comment Endogenous ACE2 improved lipid metabolism through the IKKbeta/NFkappaB/IRS-1 pathway in skeletal muscle.
Formal Description
Interaction-ID: 116082

gene/protein

ACE2

increases_activity of

process

IKBKB/NFKB1/IRS1 signaling

in mouse skeletal muscle in vivo and in vitro; improving the lipid metabolism
Drugbank entries Show/Hide entries for ACE2
Comment In this study, the mRNA levels of GRP78, ATF4 and XBP-1 were increased in the ACE2 knockout mice. Consistently, the protein levels of GRP78, eIF2alpha, ATF4, and CHOP were all significantly up-regulated in the skeletal muscle of the ACE2 KO mice.
Formal Description
Interaction-ID: 116083

organism model

ACE2 KO mouse

increases_expression of

gene/protein

HSPA5

in the skeletal muscle of ACE2 KO mice; concerning the mRNA and protein level
Drugbank entries Show/Hide entries for HSPA5
Comment ACE2 deficiency in vivo displayed lipid accumulation, ER stress and mitochondrial dysfunction in skeletal muscle.
Formal Description
Interaction-ID: 116084

phenotype

ACE2 deficiency

increases_activity of

in vivo in mouse skeletal muscle, in ACE2 knockout mice
Comment Activation of ACE2 can ameliorate ER stress and mitochondrial function, which slightly accompanied by reduced TG content and down-regulated the expression of skeletal muscle lipogenic proteins in the db/db mice.
Formal Description
Interaction-ID: 116085

gene/protein

ACE2

increases_activity of

cellular component

mitochondrion

ameliorating mitochondrial function via activation of ACE2
Drugbank entries Show/Hide entries for ACE2
Comment Activation of ACE2 can ameliorate ER stress and mitochondrial function, which slightly accompanied by reduced triglyceride (TG) content and down-regulated the expression of skeletal muscle lipogenic proteins in the db/db mice.
Formal Description
Interaction-ID: 116086

gene/protein

ACE2

decreases_quantity of

drug/chemical compound

Triacylglycerol

in db/db mice; slightly reducing TG content via activation of ACE2
Drugbank entries Show/Hide entries for ACE2
Comment Activation of ACE2 can ameliorate ER stress and mitochondrial function, which slightly accompanied by reduced triglyceride (TG) content and down-regulated the expression of skeletal muscle lipogenic proteins in the db/db mice.
Formal Description
Interaction-ID: 116087

gene/protein

ACE2

decreases_expression of

gene/protein

lipogenic proteins

in db/db mice; down-regulated expression of skeletal muscle lipogenic proteins via activation of ACE2
Drugbank entries Show/Hide entries for ACE2
Comment ER stress in the skeletal muscle was examined. During the ER stress, several specific proteins were highly expressed, including GRP78, pancreatic endoplasmic reticulum kinase-eukaryotic translation initiation factor 2alpha (eIF2alpha), binding immunoglobulin protein (BiP), also known as inositol requiring enzyme 1 alpha (IRE 1alpha)-X-box-binding protein-1 (XBP-1), activating transcription factor 4 (ATF4), and CHOP.
Formal Description
Interaction-ID: 116088

increases_expression of

gene/protein

XBP1

during ER stress
Comment ER stress in the skeletal muscle was examined. During the ER stress, several specific proteins were highly expressed, including GRP78, pancreatic endoplasmic reticulum kinase-eukaryotic translation initiation factor 2alpha (eIF2alpha), binding immunoglobulin protein (BiP), also known as inositol requiring enzyme 1 alpha (IRE 1alpha)-X-box-binding protein-1 (XBP-1), activating transcription factor 4 (ATF4), and CHOP.
Formal Description
Interaction-ID: 116089

increases_expression of

gene/protein

EIF2S1

during ER stress, concerning pancreatic endoplasmic reticulum kinase-eukaryotic translation initiation factor 2 alpha
Comment ER stress in the skeletal muscle was examined. During the ER stress, several specific proteins were highly expressed, including GRP78, pancreatic endoplasmic reticulum kinase-eukaryotic translation initiation factor 2alpha (eIF2alpha), binding immunoglobulin protein (BiP), also known as inositol requiring enzyme 1 alpha (IRE 1alpha)-X-box-binding protein-1 (XBP-1), activating transcription factor 4 (ATF4), and CHOP.
Formal Description
Interaction-ID: 116090

increases_expression of

gene/protein

ATF4

during ER stress
Comment ER stress in the skeletal muscle was examined. During the ER stress, several specific proteins were highly expressed, including GRP78, pancreatic endoplasmic reticulum kinase-eukaryotic translation initiation factor 2 alpha (eIF2alpha), binding immunoglobulin protein (BiP), also known as inositol requiring enzyme 1 alpha (IRE 1alpha)-X-box-binding protein-1 (XBP-1), activating transcription factor 4 (ATF4), and CHOP.
Formal Description
Interaction-ID: 116091

increases_expression of

gene/protein

DDIT3

during ER stress
Comment ER stress in the skeletal muscle was examined. During the ER stress, several specific proteins were highly expressed, including GRP78, pancreatic endoplasmic reticulum kinase-eukaryotic translation initiation factor 2alpha (eIF2alpha), binding immunoglobulin protein (BiP), also known as inositol requiring enzyme 1 alpha (IRE 1alpha)-X-box-binding protein-1 (XBP-1), activating transcription factor 4 (ATF4), and CHOP.
Formal Description
Interaction-ID: 116092

increases_expression of

gene/protein

HSPA5

during ER stress
Drugbank entries Show/Hide entries for HSPA5
Comment In this study, the mRNA levels of GRP78, ATF4 and XBP-1 were increased in the ACE2 knockout mice. Consistently, the protein levels of GRP78, eIF2alpha, ATF4, and CHOP were all significantly up-regulated in the skeletal muscle of the ACE2 KO mice.
Formal Description
Interaction-ID: 116093

organism model

ACE2 KO mouse

increases_expression of

gene/protein

ATF4

in the skeletal muscle of ACE2 KO mice; concerning the mRNA and protein level
Comment In this study, the mRNA levels of GRP78, ATF4 and XBP-1 were increased in the ACE2 knockout mice. Consistently, the protein levels of GRP78, eIF2alpha, ATF4, and CHOP were all significantly up-regulated in the skeletal muscle of the ACE2 KO mice.
Formal Description
Interaction-ID: 116094

organism model

ACE2 KO mouse

increases_expression of

gene/protein

XBP1

in the skeletal muscle of ACE2 KO mice; concerning the mRNA and protein level
Comment In this study, the mRNA levels of GRP78, ATF4 and XBP-1 were increased in the ACE2 knockout mice. Consistently, the protein levels of GRP78, eIF2alpha, ATF4, and CHOP were all significantly up-regulated in the skeletal muscle of the ACE2 KO mice.
Formal Description
Interaction-ID: 116095

organism model

ACE2 KO mouse

increases_quantity of

gene/protein

EIF2S1

in the skeletal muscle of ACE2 KO mice; concerning the protein level
Comment In this study, the mRNA levels of GRP78, ATF4 and XBP-1 were increased in the ACE2 knockout mice. Consistently, the protein levels of GRP78, eIF2alpha, ATF4, and CHOP were all significantly up-regulated in the skeletal muscle of the ACE2 KO mice.
Formal Description
Interaction-ID: 116096

organism model

ACE2 KO mouse

increases_quantity of

gene/protein

DDIT3

in the skeletal muscle of ACE2 KO mice; concerning the protein level
Comment The ACE2 mRNA levels were indeed reduced in the skeletal muscle of the ACE2 KO mice. They exhibited breakage of fibers and disorder of morphology. The skeletal muscle TG content was significantly higher in ACE2 KO mice than in WT mice.
Formal Description
Interaction-ID: 116098

organism model

ACE2 KO mouse

decreases_expression of

gene/protein

ACE2

in the skeletal muscle of the ACE2 KO mice; concerning ACE2 mRNA content
Drugbank entries Show/Hide entries for ACE2
Comment The ACE2 mRNA levels were indeed reduced in the skeletal muscle of the ACE2 KO mice. They exhibited breakage of fibers and disorder of morphology. The skeletal muscle TG content was significantly higher in ACE2 KO mice than in WT mice.
Formal Description
Interaction-ID: 116099

organism model

ACE2 KO mouse

increases_activity of

in the skeletal muscle of the ACE2 KO mice; concerning breakage of fibers and disorder of morphology
Comment The ACE2 mRNA levels were indeed reduced in the skeletal muscle of the ACE2 KO mice. They exhibited breakage of fibers and disorder of morphology. The skeletal muscle triglyceride (TG) content was significantly higher in ACE2 KO mice than in WT mice.
Formal Description
Interaction-ID: 116100

organism model

ACE2 KO mouse

increases_quantity of

drug/chemical compound

Triacylglycerol

in the skeletal muscle of the ACE2 KO mice
Comment The mRNA levels of fatty acid oxidation-related genes, including PPARgamma coactivator1alpha (PGC-1alpha), peroxisome proliferator-activated receptor alpha (PPARalpha), and medium chain acyl-CoA dehydrogenase (MCAD) were down-regulated, and little change was observed in PPAR gamma (PPARgamma) and CPT1A in the skeletal muscle of the ACE2 KO mice. These results suggested that deletion of ACE2 may aggravate intramuscular fat accumulate in the ACE2 KO mice.
Formal Description
Interaction-ID: 116101

organism model

ACE2 KO mouse

decreases_expression of

gene/protein

PPARGC1A

in the skeletal muscle of the ACE2 KO mice; concerning the mRNA level of PGC-1alpha
Comment The mRNA levels of fatty acid oxidation-related genes, including PPARgamma coactivator1alpha (PGC-1alpha), peroxisome proliferator-activated receptor alpha (PPARalpha), and medium chain acyl-CoA dehydrogenase (MCAD) were down-regulated, and little change was observed in PPAR gamma (PPARgamma) and CPT1A in the skeletal muscle of the ACE2 KO mice. These results suggested that deletion of ACE2 may aggravate intramuscular fat accumulate in the ACE2 KO mice.
Formal Description
Interaction-ID: 116102

organism model

ACE2 KO mouse

decreases_expression of

gene/protein

PPARA

in the skeletal muscle of the ACE2 KO mice; concerning the mRNA level of PGC-1alpha
Drugbank entries Show/Hide entries for PPARA
Comment The mRNA levels of fatty acid oxidation-related genes, including PPARgamma coactivator1alpha (PGC-1alpha), peroxisome proliferator-activated receptor alpha (PPARalpha), and medium chain acyl-CoA dehydrogenase (MCAD) were down-regulated, and little change was observed in PPAR gamma (PPARgamma) and CPT1A in the skeletal muscle of the ACE2 KO mice. These results suggested that deletion of ACE2 may aggravate intramuscular fat accumulate in the ACE2 KO mice.
Formal Description
Interaction-ID: 116103

organism model

ACE2 KO mouse

decreases_expression of

gene/protein

ACADM

in the skeletal muscle of the ACE2 KO mice; concerning the mRNA level of PGC-1alpha
Drugbank entries Show/Hide entries for ACADM
Comment To study whether the mitochondrial function affect the skeletal muscle lipid metabolism, the gene levels of mitochondrial complexes I-III were measured in ACE2 KO mice. As expected, the mRNA levels of NDUFB8 (Complex I), succinate dehydrogenase subunit B (SDHB) (Complex II), and ubiquinol-cytochrome c reductase complex core protein 2 (UQCRC2) (Complex III) were down-regulated significantly, whereas no observable difference was detected in mitochondrial encoded NADH dehydrogenase 1 (mt-ND1) group.
Formal Description
Interaction-ID: 116104

organism model

ACE2 KO mouse

decreases_expression of

gene/protein

NDUFB8

in the skeletal muscle of the ACE2 KO mice; concerning the mRNA level of NDUFB8 (Complex I)
Drugbank entries Show/Hide entries for NDUFB8
Comment To study whether the mitochondrial function affect the skeletal muscle lipid metabolism, the gene levels of mitochondrial complexes I-III were measured in ACE2 KO mice. As expected, the mRNA levels of NDUFB8 (Complex I), succinate dehydrogenase subunit B (SDHB) (Complex II), and ubiquinol-cytochrome c reductase complex core protein 2 (UQCRC2) (Complex III) were down-regulated significantly, whereas no observable difference was detected in mitochondrial encoded NADH dehydrogenase 1 (mt-ND1) group.
Formal Description
Interaction-ID: 116105

organism model

ACE2 KO mouse

decreases_expression of

gene/protein

SDHB

in the skeletal muscle of the ACE2 KO mice; concerning the mRNA level of SDHB (Complex II)
Drugbank entries Show/Hide entries for SDHB
Comment To study whether the mitochondrial function affect the skeletal muscle lipid metabolism, the gene levels of mitochondrial complexes I-III were measured in ACE2 KO mice. As expected, the mRNA levels of NDUFB8 (Complex I), succinate dehydrogenase subunit B (SDHB) (Complex II), and ubiquinol-cytochrome c reductase complex core protein 2 (UQCRC2) (Complex III) were down-regulated significantly, whereas no observable difference was detected in mitochondrial encoded NADH dehydrogenase 1 (mt-ND1) group.
Formal Description
Interaction-ID: 116106

organism model

ACE2 KO mouse

decreases_expression of

gene/protein

UQCRC2

in the skeletal muscle of the ACE2 KO mice; concerning the mRNA level of UQCRC2 (Complex III)
Drugbank entries Show/Hide entries for UQCRC2
Comment ACE2 was overexpressed in the C2C12 cells to evaluate its role in lipid metabolism and ER stress by RT-PCR analysis in vitro. Firstly, ACE2 has been proved to be indeed overexpressed after the adenoviruses infect. Secondly, the mRNA levels of fatty acid oxidation-related genes, PPARalpha, PPARgamma, and CPT1A were increased, and little change was observed in PGC-1alpha and MCAD in ACE2-overexpressing C2C12 cells. The results showed that the overexpression of ACE2 significantly improved fatty acid oxidation and ER stress.
Formal Description
Interaction-ID: 116107

gene/protein

ACE2

increases_expression of

gene/protein

PPARA

in ACE2-overexpressing C2C12 cells; concerning PPARA mRNA; ACE2 has also been proved to be overexpressed after the adenoviruses infect
Drugbank entries Show/Hide entries for ACE2 or PPARA
Comment ACE2 was overexpressed in the C2C12 cells to evaluate its role in lipid metabolism and ER stress by RT-PCR analysis in vitro. Firstly, ACE2 has been proved to be indeed overexpressed after the adenoviruses infect. Secondly, the mRNA levels of fatty acid oxidation-related genes, PPARalpha, PPARgamma, and CPT1A were increased, and little change was observed in PGC-1alpha and MCAD in ACE2-overexpressing C2C12 cells. The results showed that the overexpression of ACE2 significantly improved fatty acid oxidation and ER stress.
Formal Description
Interaction-ID: 116108

gene/protein

ACE2

increases_expression of

gene/protein

PPARG

in ACE2-overexpressing C2C12 cells; concerning PPARG mRNA; ACE2 has also been proved to be overexpressed after the adenoviruses infect
Drugbank entries Show/Hide entries for ACE2 or PPARG
Comment ACE2 was overexpressed in the C2C12 cells to evaluate its role in lipid metabolism and ER stress by RT-PCR analysis in vitro. Firstly, ACE2 has been proved to be indeed overexpressed after the adenoviruses infect. Secondly, the mRNA levels of fatty acid oxidation-related genes, PPARalpha, PPARgamma, and CPT1A were increased, and little change was observed in PGC-1alpha and MCAD in ACE2-overexpressing C2C12 cells. The results showed that the overexpression of ACE2 significantly improved fatty acid oxidation and ER stress.
Formal Description
Interaction-ID: 116109

gene/protein

ACE2

increases_expression of

gene/protein

CPT1A

in ACE2-overexpressing C2C12 cells; concerning CPT1A mRNA; ACE2 has also been proved to be overexpressed after the adenoviruses infect
Drugbank entries Show/Hide entries for ACE2 or CPT1A
Comment The results showed that the overexpression of ACE2 in the C2C12 cells significantly improved fatty acid oxidation and ER stress.
Formal Description
Interaction-ID: 116110

gene/protein

ACE2

increases_activity of

in ACE2-overexpressing C2C12 cells
Drugbank entries Show/Hide entries for ACE2
Comment ACE2 was first reported to play a notable role on intramuscular fat regulation by improving endoplasmic reticulum and mitochondrial function.
Formal Description
Interaction-ID: 116113

gene/protein

ACE2

increases_activity of

cellular component

endoplasmic reticulum

playing a notable role on intramuscular fat regulation by improving endoplasmic reticulum and mitochondrial function
Drugbank entries Show/Hide entries for ACE2
Comment The results showed that the overexpression of ACE2 in the C2C12 cells significantly improved fatty acid oxidation and ER stress.
Formal Description
Interaction-ID: 116114

gene/protein

ACE2

decreases_activity of

in ACE2-overexpressing C2C12 cells
Drugbank entries Show/Hide entries for ACE2
Comment ACE2 was first reported to play a notable role on intramuscular fat regulation by improving endoplasmic reticulum and mitochondrial function.
Formal Description
Interaction-ID: 116115

gene/protein

ACE2

increases_activity of

cellular component

mitochondrion

playing a notable role on intramuscular fat regulation by improving endoplasmic reticulum and mitochondrial function
Drugbank entries Show/Hide entries for ACE2
Comment Endogenous ACE2 improved lipid metabolism through the IKKbeta/NFkappaB/IRS-1 pathway in skeletal muscle.
Formal Description
Interaction-ID: 116116

process

IKBKB/NFKB1/IRS1 signaling

increases_activity of

in mouse skeletal muscle in vivo and in vitro
Comment To explore a possible mechanism involvement of ACE2 in its beneficial effect against ER stress, the expression of the IKKbeta/NFkappaB pathway in the ACE2 KO mice was evaluated and found that the levels of phosphorylated NFkappaB and IKKbeta markedly increased. Although the total amount of NFkappaB and IKKbeta protein did not change.
Formal Description
Interaction-ID: 116122

organism model

ACE2 KO mouse

increases_phosphorylation of

gene/protein

NFKB1

in the ACE2 KO mice; but the total amount of NFkappaB and IKKbeta protein did not change
Drugbank entries Show/Hide entries for NFKB1
Comment To explore a possible mechanism involvement of ACE2 in its beneficial effect against ER stress, the expression of the IKKbeta/NFkappaB pathway in the ACE2 KO mice was evaluated and found that the levels of phosphorylated NFkappaB and IKKbeta markedly increased. Although the total amount of NFkappaB and IKKbeta protein did not change.
Formal Description
Interaction-ID: 116123

organism model

ACE2 KO mouse

increases_phosphorylation of

gene/protein

IKBKB

in the ACE2 KO mice; but the total amount of NFkappaB and IKKbeta protein did not change
Drugbank entries Show/Hide entries for IKBKB
Comment To explore a possible mechanism involvement of ACE2 in its beneficial effect against ER stress, the expression of the IKKbeta/NFkappaB pathway in the ACE2 KO mice was evaluated and found that the levels of phosphorylated NFkappaB and IKKbeta markedly increased. Although the total amount of NFkappaB and IKKbeta protein did not change.
Formal Description
Interaction-ID: 116124

organism model

ACE2 KO mouse

increases_quantity of

protein modification

NFKB1-phos

in the ACE2 KO mice; but the total amount of NFkappaB and IKKbeta protein did not change
Comment To explore a possible mechanism involvement of ACE2 in its beneficial effect against ER stress, the expression of the IKKbeta/NFkappaB pathway in the ACE2 KO mice was evaluated and found that the levels of phosphorylated NFkappaB and IKKbeta markedly increased. Although the total amount of NFkappaB and IKKbeta protein did not change.
Formal Description
Interaction-ID: 116125

organism model

ACE2 KO mouse

increases_quantity of

protein modification

IKBKB-phos

in the ACE2 KO mice; but the total amount of NFkappaB and IKKbeta protein did not change
Comment The protein levels of lipid-metabolizing genes, including ACCalpha and SREBP-1c were up-regulated, whereas the expression of LXRalpha and CPT-1A did not exhibit an obvious difference between the ACE2 KO mice and the WT groups.
Formal Description
Interaction-ID: 116136

organism model

ACE2 KO mouse

increases_quantity of

gene/protein

ACACA

in the ACE2 KO mice; concerning the protein level, compared to WT
Drugbank entries Show/Hide entries for ACACA
Comment The protein levels of lipid-metabolizing genes, including ACCalpha and SREBP-1c were up-regulated, whereas the expression of LXRalpha and CPT-1A did not exhibit an obvious difference between the ACE2 KO mice and the WT groups.
Formal Description
Interaction-ID: 116137

organism model

ACE2 KO mouse

increases_quantity of

mRNA/protein variant

SREBF1c

in the ACE2 KO mice; concerning the protein level, compared to WT
Comment The protein levels of lipid-metabolizing genes, including ACCalpha and SREBP-1c were up-regulated, whereas the expression of LXRalpha and CPT-1A did not exhibit an obvious difference between the ACE2 KO mice and the WT groups.
Formal Description
Interaction-ID: 116138

organism model

ACE2 KO mouse

NOT affects_quantity of

gene/protein

NR1H3

in the ACE2 KO mice; concerning the protein level, compared to WT
Drugbank entries Show/Hide entries for NR1H3
Comment The protein levels of lipid-metabolizing genes, including ACCalpha and SREBP-1c were up-regulated, whereas the expression of LXRalpha and CPT-1A did not exhibit an obvious difference between the ACE2 KO mice and the WT groups.
Formal Description
Interaction-ID: 116139

organism model

ACE2 KO mouse

NOT affects_quantity of

gene/protein

CPT1A

in the ACE2 KO mice; concerning the protein level, compared to WT
Drugbank entries Show/Hide entries for CPT1A
Comment Some key transcriptional regulators, such as LXRalpha and SREBP-1c, coordinately control the lipogenesis, which increase the expression of key lipogenic genes, including those for FAS, SCD1 and ACC. (cited information)
Formal Description
Interaction-ID: 116140

gene/protein

NR1H3

increases_activity of

LXRalpha and SREBP-1c, as key transcriptional regulators, coordinately control the lipogenesis
Drugbank entries Show/Hide entries for NR1H3
Comment Some key transcriptional regulators, such as LXRalpha and SREBP-1c, coordinately control the lipogenesis, which increase the expression of key lipogenic genes, including those for FAS, SCD1 and ACC. (cited information)
Formal Description
Interaction-ID: 116141

mRNA/protein variant

SREBF1c

increases_activity of

LXRalpha and SREBP-1c, as key transcriptional regulators, coordinately control the lipogenesis
Comment The protein levels of lipogenesis proteins ACCalpha and SREBP-1C increased in the ACE2 KO mice, and decreased in the ACE2-overexpressing db/db mice. These results suggested that ACE2 may regulate intramuscular fat accumulate in mice.
Formal Description
Interaction-ID: 116142

gene/protein

ACE2

decreases_quantity of

gene/protein

ACACA

in ACE2-overexpressing db/db mice
Drugbank entries Show/Hide entries for ACE2 or ACACA
Comment The protein levels of lipogenesis proteins ACCalpha and SREBP-1C increased in the ACE2 KO mice, and decreased in the ACE2-overexpressing db/db mice. These results suggested that ACE2 may regulate intramuscular fat accumulate in mice.
Formal Description
Interaction-ID: 116143

gene/protein

ACE2

decreases_quantity of

mRNA/protein variant

SREBF1

in ACE2-overexpressing db/db mice
Drugbank entries Show/Hide entries for ACE2
Comment ACE2 deficiency in vivo displayed lipid accumulation, ER stress and mitochondrial dysfunction in skeletal muscle.
Formal Description
Interaction-ID: 116929

gene/protein

ACE2

decreases_activity of

reasoned via ACE2 KO mice in skeletal muscles
Drugbank entries Show/Hide entries for ACE2
Comment It is demonstrated that alterations in mitochondria and ER physical interactions contribute to insulin resistance. Indeed, mitochondria and ER interact at contact points, called mitochondria-associated endoplasmic reticulum membranes (MAMs), in order to exchange calcium (Ca2+) and lipids, thus regulating cell metabolism and fate. (cited information)
Formal Description
Interaction-ID: 119588

affects_activity of

phenotype

insulin resistance

alterations in mitochondria and ER physical interactions contribute to insulin resistance
Comment It is demonstrated that alterations in mitochondria and ER physical interactions contribute to insulin resistance. Indeed, mitochondria and ER interact at contact points, called mitochondria-associated endoplasmic reticulum membranes (MAMs), in order to exchange calcium (Ca2+) and lipids, thus regulating cell metabolism and fate. (cited information)
Formal Description
Interaction-ID: 119602

phenotype

altered mitochondria-associated endoplasmic reticulum membrane interaction

increases_activity of

phenotype

insulin resistance

alterations in mitochondria and ER physical interactions contribute to insulin resistance
Comment It is demonstrated that alterations in mitochondria and ER physical interactions contribute to insulin resistance. Indeed, mitochondria and ER interact at contact points, called mitochondria-associated endoplasmic reticulum membranes (MAMs), in order to exchange calcium (Ca2+) and lipids, thus regulating cell metabolism and fate. (cited information)
Formal Description
Interaction-ID: 119608

cellular component

mitochondrion

interacts (colocalizes) with

mitochondria and ER interact at contact points, called mitochondria-associated endoplasmic reticulum membranes (MAMs), in order to exchange calcium (Ca2+) and lipids, thus regulating cell metabolism and fate
Comment It is demonstrated that alterations in mitochondria and ER physical interactions contribute to insulin resistance. Indeed, mitochondria and ER interact at contact points, called mitochondria-associated endoplasmic reticulum membranes (MAMs), in order to exchange calcium (Ca2+) and lipids, thus regulating cell metabolism and fate. (cited information)
Formal Description
Interaction-ID: 119610

cellular component

endoplasmic reticulum

interacts (colocalizes) with

mitochondria and ER interact at contact points, called mitochondria-associated endoplasmic reticulum membranes (MAMs), in order to exchange calcium (Ca2+) and lipids, thus regulating cell metabolism and fate
Comment In consequence of ER stress, an adaptive process named UPR (unfolded protein response) is triggered. Three distinct branches of the UPR system can be initiated by transmembrane effector signal transduction proteins-protein kinase R (PKR)-like ER kinase (PERK), inositol requiring enzyme 1 alpha (IRE1alpha), and activating transcription factor 6 (ATF6). The UPR consists of three signaling branches which are initiated by signals such as the dissociation of BiP (GRP78) from the intracellular receptor domains of the ER. These signals activate combinations of the three stress sensors, protein kinase RNA-like PERK, ATF6 and inositol-requiring enzyme 1alpha (IRE 1alpha). CHOP is a downstream effector of all the three branches of the UPR. Enhanced CHOP expression has several effects on cells including alteration of the balance of pro- and anti-apoptotic proteins that act on mitochondria. In RAS, Ang II and ACE2 have been reported to induce ER stress via GRP78/eIF2alpha/ATF4/CHOP axis in the liver. (cited information)
Formal Description
Interaction-ID: 119612
Comment The protein levels of GRP78, eIF2alpha, ATF4, and CHOP were all significantly up-regulated in the skeletal muscle of the ACE2 KO mice.
Formal Description
Interaction-ID: 120293

gene/protein

ACE2

decreases_quantity of

gene/protein

HSPA5

in the skeletal muscle of ACE2 KO mice; GRP78 protein was up-regulated
Drugbank entries Show/Hide entries for ACE2 or HSPA5
Comment In this study, the mRNA levels of GRP78, ATF4 and XBP-1 were increased in the ACE2 knockout mice. Consistently, the protein levels of GRP78, eIF2alpha, ATF4, and CHOP were all significantly up-regulated in the skeletal muscle of the ACE2 KO mice.
Formal Description
Interaction-ID: 136262

organism model

ACE2 KO mouse

increases_quantity of

gene/protein

HSPA5

in the skeletal muscle of ACE2 KO mice; concerning the mRNA and protein level
Drugbank entries Show/Hide entries for HSPA5
Comment In this study, the mRNA levels of GRP78, ATF4 and XBP-1 were increased in the ACE2 knockout mice. Consistently, the protein levels of GRP78, eIF2alpha, ATF4, and CHOP were all significantly up-regulated in the skeletal muscle of the ACE2 KO mice.
Formal Description
Interaction-ID: 136263

organism model

ACE2 KO mouse

increases_quantity of

gene/protein

ATF4

in the skeletal muscle of ACE2 KO mice; concerning the mRNA and protein level
Comment In this study, the mRNA levels of GRP78, ATF4 and XBP-1 were increased in the ACE2 knockout mice. Consistently, the protein levels of GRP78, eIF2alpha, ATF4, and CHOP were all significantly up-regulated in the skeletal muscle of the ACE2 KO mice.
Formal Description
Interaction-ID: 136264

organism model

ACE2 KO mouse

increases_quantity of

gene/protein

XBP1

in the skeletal muscle of ACE2 KO mice; concerning the mRNA and protein level
Comment In this study, the mRNA levels of GRP78, ATF4 and XBP-1 were increased in the ACE2 knockout mice. Consistently, the protein levels of GRP78, eIF2alpha, ATF4, and CHOP were all significantly up-regulated in the skeletal muscle of the ACE2 KO mice.
Formal Description
Interaction-ID: 136265

organism model

ACE2 KO mouse

increases_quantity of

gene/protein

EIF2S1

in the skeletal muscle of ACE2 KO mice; concerning the protein level
Comment In this study, the mRNA levels of GRP78, ATF4 and XBP-1 were increased in the ACE2 knockout mice. Consistently, the protein levels of GRP78, eIF2alpha, ATF4, and CHOP were all significantly up-regulated in the skeletal muscle of the ACE2 KO mice.
Formal Description
Interaction-ID: 136266

organism model

ACE2 KO mouse

increases_quantity of

gene/protein

DDIT3

in the skeletal muscle of ACE2 KO mice; concerning the protein level
Comment In this study, the mRNA levels of GRP78, ATF4 and XBP-1 were increased in the ACE2 knockout mice. Consistently, the protein levels of GRP78, eIF2alpha, ATF4, and CHOP were all significantly up-regulated in the skeletal muscle of the ACE2 KO mice.
Formal Description
Interaction-ID: 136845

organism model

ACE2 KO mouse

increases_activity of

phenotype

ACE2 deficiency

in the skeletal muscle of ACE2 KO mice; concerning the mRNA and protein level