Metformin attenuated endotoxin-induced acute myocarditis via activating AMPK
Copyright © 2017 Elsevier B.V. All rights reserved..
Metformin is a widely used anti-diabetic drug and increasing evidence suggests that metformin have profound cardioprotective effects under both diabetic and non-diabetic situations. The protective benefits of metformin have been proved in diabetic patients with cardiovascular complications and in experimental animals with myocardial infarction and cardiac hypertrophy. In the present study, we found that treatment with metformin inhibited the cardiac expression of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and interleukin 6 (IL-6) in endotoxin-challenged mice. Treatment with metformin also alleviated the histological abnormalities in the heart, suppressed the upregulation of myeloperoxidase (MPO), decreased the elevation of creatinine kinase-myocardial band (CK-MB) and brain natriuretic peptide (BNP). Treatment with metformin promoted the phosphorylation of the catalytic α subunit of adenosine 5'-monophosphate-activated protein kinase (AMPKα), co-administration of AMPK inhibitor suppressed the stimulatory effects of metformin on AMPKα phosphorylation. Meanwhile, the suppressive effects of metformin on MPO, TNF-α, CK-MB and BNP were reversed by the AMPK inhibitor. On the contrary, administration of AMPK activator mimicked the effects of metformin on AMPKα phosphorylation, MPO upregulation, CK-MB release and BNP elevation. These evidence suggested that metformin might provide beneficial effects in endotoxin-induced acute myocarditis via activating AMPK-dependent anti-inflammatory mechanism.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2017 |
|---|---|
| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:47 |
|---|---|
| Enthalten in: |
International immunopharmacology - 47(2017) vom: 01. Juni, Seite 166-172 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Liu, Gang [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 26.03.2018 Date Revised 26.03.2018 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.intimp.2017.04.002 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM270977171 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM270977171 | ||
| 003 | DE-627 | ||
| 005 | 20231224231721.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2017 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.intimp.2017.04.002 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0903.xml |
| 035 | |a (DE-627)NLM270977171 | ||
| 035 | |a (NLM)28410530 | ||
| 035 | |a (PII)S1567-5769(17)30136-4 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Liu, Gang |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Metformin attenuated endotoxin-induced acute myocarditis via activating AMPK |
| 264 | 1 | |c 2017 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 26.03.2018 | ||
| 500 | |a Date Revised 26.03.2018 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2017 Elsevier B.V. All rights reserved. | ||
| 520 | |a Metformin is a widely used anti-diabetic drug and increasing evidence suggests that metformin have profound cardioprotective effects under both diabetic and non-diabetic situations. The protective benefits of metformin have been proved in diabetic patients with cardiovascular complications and in experimental animals with myocardial infarction and cardiac hypertrophy. In the present study, we found that treatment with metformin inhibited the cardiac expression of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and interleukin 6 (IL-6) in endotoxin-challenged mice. Treatment with metformin also alleviated the histological abnormalities in the heart, suppressed the upregulation of myeloperoxidase (MPO), decreased the elevation of creatinine kinase-myocardial band (CK-MB) and brain natriuretic peptide (BNP). Treatment with metformin promoted the phosphorylation of the catalytic α subunit of adenosine 5'-monophosphate-activated protein kinase (AMPKα), co-administration of AMPK inhibitor suppressed the stimulatory effects of metformin on AMPKα phosphorylation. Meanwhile, the suppressive effects of metformin on MPO, TNF-α, CK-MB and BNP were reversed by the AMPK inhibitor. On the contrary, administration of AMPK activator mimicked the effects of metformin on AMPKα phosphorylation, MPO upregulation, CK-MB release and BNP elevation. These evidence suggested that metformin might provide beneficial effects in endotoxin-induced acute myocarditis via activating AMPK-dependent anti-inflammatory mechanism | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a AMP-activated protein kinase | |
| 650 | 4 | |a Endotoxin | |
| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a Metformin | |
| 650 | 4 | |a Myocarditis | |
| 650 | 7 | |a Anti-Inflammatory Agents |2 NLM | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a Inflammation Mediators |2 NLM | |
| 650 | 7 | |a Lipopolysaccharides |2 NLM | |
| 650 | 7 | |a Natriuretic Peptide, Brain |2 NLM | |
| 650 | 7 | |a 114471-18-0 |2 NLM | |
| 650 | 7 | |a Metformin |2 NLM | |
| 650 | 7 | |a 9100L32L2N |2 NLM | |
| 650 | 7 | |a Peroxidase |2 NLM | |
| 650 | 7 | |a EC 1.11.1.7 |2 NLM | |
| 650 | 7 | |a AMPK alpha1 subunit, mouse |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a AMP-Activated Protein Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.31 |2 NLM | |
| 700 | 1 | |a Wu, Kejia |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Dai, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Ge, Pu |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Fuling |e verfasserin |4 aut | |
| 700 | 1 | |a Lei, Han |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International immunopharmacology |d 2001 |g 47(2017) vom: 01. Juni, Seite 166-172 |w (DE-627)NLM112639542 |x 1878-1705 |7 nnns |
| 773 | 1 | 8 | |g volume:47 |g year:2017 |g day:01 |g month:06 |g pages:166-172 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.intimp.2017.04.002 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 47 |j 2017 |b 01 |c 06 |h 166-172 | ||