Activation of AMP‐activated protein kinase by metformin ablates angiotensin II‐induced endoplasmic reticulum stress and hypertension in mice <i>in vivo</i>

Duan, Qing; Song, Ping; Ding, Ye

doi:10.1111/bph.13833

Cited by 45 publications

(33 citation statements)

References 79 publications

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“…In Nagata et al's [91] research, they found that AngII could activate AMPK, but the test was performed within 1 h, and if they extend the duration of action, will the results change? In another study, low concentrations (0.1-1 μM) of AngII led to minor activation of AMPK, whereas high concentrations (5 μM) of AngII decreased AMPKα phosphorylation in human VSMCs [93]. We hypothesize that AngII activates AMPK at a small initial dose and protects it.…”

Section: Angii and Ampk In Kidneymentioning

confidence: 80%

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AMPK: a balancer of the renin–angiotensin system

Liu

et al. 2019

Bioscience Reports

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The renin–angiotensin system (RAS) is undisputedly well-studied as one of the oldest and most critical regulators for arterial blood pressure, fluid volume, as well as renal function. In recent studies, RAS has also been implicated in the development of obesity, diabetes, hyperlipidemia, and other diseases, and also involved in the regulation of several signaling pathways such as proliferation, apoptosis and autophagy, and insulin resistance. AMP-activated protein kinase (AMPK), an essential cellular energy sensor, has also been discovered to be involved in these diseases and cellular pathways. This would imply a connection between the RAS and AMPK. Therefore, this review serves to draw attention to the cross-talk between RAS and AMPK, then summering the most recent literature which highlights AMPK as a point of balance between physiological and pathological functions of the RAS.

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Section: Angii and Ampk In Kidneymentioning

confidence: 80%

“…While they did not detect the RAS components in this experiment. Later studies showed that when the treating time and concentration are sufficient, AngII tended to suppress the activity of AMPK [92,93]. There was another study, which declaimed AngII could elevate LKB1 expression in VSMCs and neointima.…”

Section: Angii and Ampk In The Vascular Systemmentioning

confidence: 99%

AMPK: a balancer of the renin–angiotensin system

Liu

et al. 2019

Bioscience Reports

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“…28 Metformin treatment decreases angiotensin II-induced ER stress and hypertension in mice through activation of AMPK. 29 Metformin also decreases β-cell lipotoxicity through inhibition of the ER stress. 30 Pathologic ER stress leads to calcium release, which is directed toward the mitochondria via domains shared by ER and mitochondria called mitochondria-associated membranes (MAM).…”

mentioning

confidence: 99%

Metformin attenuates ER stress–induced mitochondrial dysfunction

Chen

Thompson

et al. 2017

Translational Research

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Endoplasmic reticulum (ER) stress, a disturbance of the ER function, contributes to cardiac injury. ER and mitochondria are closely connected organelles within cells. ER stress contributes to mitochondrial dysfunction, which is a key factor to increase cardiac injury. Metformin, a traditional anti-diabetic drug, decreases cardiac injury during ischemia-reperfusion. Metformin also inhibits ER stress in cultured cells. We hypothesized that metformin can attenuate the ER stress-induced mitochondrial dysfunction and subsequent cardiac injury. Thapsigargin (THAP, 3 mg/kg) was used to induce ER stress in C57BL/6 mice. Cell injury and mitochondrial function were evaluated in the mouse heart 48 hours after one-time THAP treatment. Metformin was dissolved in drinking water (0.5g/250 ml) and fed to mice for 7 days before THAP injection. Metformin feeding continued after THAP treatment. THAP treatment increased apoptosis in mouse myocardium compared to control. THAP also led to decreased oxidative phosphorylation in heart mitochondria oxidizing complex I substrates. THAP decreased the calcium retention capacity (CRC), indicating that ER stress sensitizes mitochondria to mitochondrial permeability transition pore opening. The cytosolic CHOP content was markedly increased in THAP-treated hearts compared to control, particularly in the nucleus. Metformin prevented the THAP-induced mitochondrial dysfunction and reduced CHOP content in cytosol and nucleus. Thus, metformin reduces cardiac injury during ER stress through the protection of cardiac mitochondria and attenuation of CHOP expression.

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“…This phosphorylation results in abnormal N-glycosylation of PD-L1 and prevents its development within the Golgi apparatus and degradation in endoplasmic reticulum. Therefore, metformin causes malignant cells to be more susceptible to cytotoxic T cells (19)(20)(21)(22).…”

Section: Methodsmentioning

confidence: 99%

Administration of metformin to increase the efficacy of chemotherapy regimen in cancers; a new look to an old drug

Hooshyar¹,

Tolouian²,

Ghasemi³

et al. 2019

Immunopathol Persa

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Chemotherapeutic agents are still the major and most common therapy to prevent tumor growth. These drugs have various adverse effects in different organs in addition to systemic effects. Finding more specific and effective drugs or new adjuvant therapeutic substance is needed to improve the success rate. Several studies have proposed the possible mechanisms of anti-neoplastic of metformin, however, its exact mechanism is still obscure. The suggested mechanisms are; alteration in the host metabolic environment after administration of metformin, such as decreases in insulin-dependent stimulation of tumor growth or direct effect on cancer cells, such as the impact on adenosine monophosphate (AMP)-activated protein kinase signaling pathway. Metformin, as an adjuvant therapy, synergistically exerts growth inhibitory effects against cell growth and can induce cell apoptosis in an animal model. Adding metformin to the chemotherapy regimen may reduce resistance and enhance therapeutic efficacy.

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Activation of AMP‐activated protein kinase by metformin ablates angiotensin II‐induced endoplasmic reticulum stress and hypertension in mice in vivo

Abstract: Metformin alleviates Ang II-triggered hypertension in mice by activating AMPKα2, which mediates phospholamban phosphorylation and inhibits Ang II-induced ER stress in vascular smooth muscle cells.

Cited by 45 publications

References 79 publications

AMPK: a balancer of the renin–angiotensin system

AMPK: a balancer of the renin–angiotensin system

Metformin attenuates ER stress–induced mitochondrial dysfunction

Administration of metformin to increase the efficacy of chemotherapy regimen in cancers; a new look to an old drug

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