AMPK contributes to aerobic exercise-induced antinociception downstream of endocannabinoids

King-Himmelreich, Tanya S.; Möser, Christine V.; Wolters, Miriam; Schmetzer, Julia; Schreiber, Yannik; Ferreiròs, Nerea; Russe, Otto Quintus; Geißlinger, Gerd; Niederberger, Ellen

doi:10.1016/j.neuropharm.2017.05.002

Cited by 20 publications

(23 citation statements)

References 39 publications

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“…As illustrated in Figure 1 , cultured H9C2 cells were randomly divided into 4 groups: control (C), H 2 O 2 (H; 50 μmol/L, a selected dose based on the above-mentioned dose-response study), AICAR (A; 1 mmol/L), and H 2 O 2 + AICAR (H + A). AICAR is widely used as an activator of AMPK, and it simulates AMPK-related metabolic effects of exercise at the cellular level [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

“…Additional series of in vitro experiments were also conducted in H9C2 rat cardiomyoblasts using 5-amino-1-β- d -ribofuranosyl-imidazole-4-carboxamide (AICAR), a widely used activator of adenosine monophosphate (AMP)-activated protein kinase (AMPK), which is an important regulator of cell metabolism and energy sensor. The use of AICAR is to simulate a common action of various types of physical exercise, i.e., AMPK activation [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

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Role of Muscle-Specific Histone Methyltransferase (Smyd1) in Exercise-Induced Cardioprotection against Pathological Remodeling after Myocardial Infarction

Liang

Cai

Zhang

et al. 2020

IJMS

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Pathological remodeling is the main detrimental complication after myocardial infarction (MI). Overproduction of reactive oxygen species (ROS) in infarcted myocardium may contribute to this process. Adequate exercise training after MI may reduce oxidative stress-induced cardiac tissue damage and remodeling. SET and MYND domain containing 1 (Smyd1) is a muscle-specific histone methyltransferase which is upregulated by resistance training, may strengthen sarcomere assembly and myofiber folding, and may promote skeletal muscles growth and hypertrophy. However, it remains elusive if Smyd1 has similar functions in post-MI cardiac muscle and participates in exercise-induced cardioprotection. Accordingly, we investigated the effects of interval treadmill exercise on cardiac function, ROS generation, Smyd1 expression, and sarcomere assembly of F-actin in normal and infarcted hearts. Adult male rats were randomly divided into five groups (n = 10/group): control (C), exercise alone (EX), sham-operated (S), MI induced by permanent ligation of left anterior descending coronary artery (MI), and MI with interval exercise training (MI + EX). Exercise training significantly improved post-MI cardiac function and sarcomere assembly of F-actin. The cardioprotective effects were associated with increased Smyd1, Trx1, cTnI, and α-actinin expression as well as upregulated ratio of phosphorylated AMP-activated protein kinase (AMPK)/AMPK, whereas Hsp90, MuRF1, brain natriuretic peptide (BNP) expression, ROS generation, and myocardial fibrosis were attenuated. The improved post-MI cardiac function was associated with increased Smyd1 expression. In cultured H9C2 cardiomyoblasts, in vitro treatment with H2O2 (50 µmol/L) or AMP-activated protein kinase (AMPK) agonist (AICAR, 1 mmol/L) or their combination for 4 h simulated the effects of exercise on levels of ROS and Smyd1. In conclusion, we demonstrated a novel role of Smyd1 in association with post-MI exercise-induced cardioprotection. The moderate level of ROS-induced upregulation of Smyd1 may be an important target for modulating post-MI cardiac function and remodeling.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of Muscle-Specific Histone Methyltransferase (Smyd1) in Exercise-Induced Cardioprotection against Pathological Remodeling after Myocardial Infarction

Liang

Cai

Zhang

et al. 2020

IJMS

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“…Interestingly, the antinociceptive effect of metformin is similar to that of exercise. Exercise leads to the increase of anandamide that in turn activates AMPK to induce antinociception (King-Himmelreich et al, 2017). This mechanism may also explain the effect of exercise in several types of pain (Slivicki et al, 2019).…”

Section: Inflammatory Painmentioning

confidence: 98%

“…Exercise improves physical function and fibromyalgia symptoms (Schachter et al, 2003). As stated above, there are some studies suggesting that physical exercise reduces weight and pain by activation of AMPK in mice with neuropathic pain (King-Himmelreich et al, 2017;Slivicki et al, 2019). Since exercise reduces nociception in neuropathic rodents and humans, it is likely that this non-pharmacological intervention could also decrease nerve injury-induced anxiety-and depression-like behaviors in neuropathic patients.…”

Section: Anxiety and Depressionmentioning

confidence: 99%

Metformin: A Prospective Alternative for the Treatment of Chronic Pain

et al. 2020

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Metformin (biguanide) is a drug widely used for the treatment of type 2 diabetes. This drug has been used for 60 years as a highly effective antihyperglycemic agent. The search for the mechanism of action of metformin has produced an enormous amount of research to explain its effects on gluconeogenesis, protein metabolism, fatty acid oxidation, oxidative stress, glucose uptake, autophagy and pain, among others. It was only up the end of the 1990s and beginning of this century that some of its mechanisms were revealed. Metformin induces its beneficial effects in diabetes through the activation of a master switch kinase named AMP-activated protein kinase (AMPK). Two upstream kinases account for the physiological activation of AMPK: liver kinase B1 and calcium/ calmodulin-dependent protein kinase kinase 2. Once activated, AMPK inhibits the mechanistic target of rapamycin complex 1 (mTORC1), which in turn avoids the phosphorylation of p70 ribosomal protein S6 kinase 1 and phosphatidylinositol 3kinase/protein kinase B signaling pathways and reduces cap-dependent translation initiation. Since metformin is a disease-modifying drug in type 2 diabetes, which reduces the mTORC1 signaling to induce its effects on neuronal plasticity, it was proposed that these mechanisms could also explain the antinociceptive effect of this drug in several models of chronic pain. These studies have highlighted the efficacy of this drug in chronic pain, such as that from neuropathy, insulin resistance, diabetic neuropathy, and fibromyalgia-type pain. Mounting evidence indicates that chronic pain may induce anxiety, depression and cognitive impairment in rodents and humans. Interestingly, metformin is able to reverse some of these consequences of pathological pain in rodents. The purpose of this review was to analyze the current evidence about the effects of metformin in chronic pain and three of its comorbidities (anxiety, depression and cognitive impairment).

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“…In the current study, we have tested a single session of exercise to the relief the hyperalgesia; however, we failed to show that. The rational to test one session of exercise as analgesic upon pain behavior was based on previous studies that have shown that single session of the exercise was able to trigger antinociceptive effect (Galdino & Romero, 2014a, 2014b; King‐Himmelreich et al., 2017).…”

Section: Discussionmentioning

confidence: 99%

Single exercise stress reduces central neurotrophins levels and adenosine A₁ and A₂ receptors expression, but does not revert opioid‐induced hyperalgesia in rats

Medeiros

Nunes

Lopes

et al. 2020

Intl J of Devlp Neuroscience

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Background This study assessed the effects of an acute stress model upon the long‐term hyperalgesia induced by repeated morphine administration in neonatal rats. We also evaluated neurotrophins and cytokines levels; expressions of adenosine and acetylcholine receptors, and acetylcholinesterase enzyme at the spinal cord. Material and methods Male Wistar rats were subjected to morphine or saline administration from P8 to P14. Thermal hyperalgesia and mechanical hyperesthesia were assessed using the hot plate (HP) and von Frey (vF) tests, respectively, at postnatal day P30 and P60. After baseline measurements, rats were subjected to a single exercise session, as an acute stress model, at P30 or P60. We measured the levels of BDNF and NGF, interleukin‐6, and IL‐10 in the cerebral cortex and the brainstem; and the expression levels of adenosine and muscarinic receptors, as well as acetylcholinesterase (AChE) enzyme at the spinal cord. Results A stress exercise session was not able to revert the morphine‐induced hyperalgesia. The morphine and exercise association in rats induced a decrease in the neurotrophins brainstem levels, and A1, A2A, A2B receptors expression in the spinal cord, and an increase in the IL‐6 cortical levels. The exercise reduced M2 receptors expression in the spinal cord of naive rats, while morphine prevented this effect. Conclusions Single session of exercise does not revert hyperalgesia induced by morphine in rats; however, morphine plus exercise modulate neurotrophins, IL‐6 central levels, and expression of adenosine receptors.

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AMPK contributes to aerobic exercise-induced antinociception downstream of endocannabinoids

Cited by 20 publications

References 39 publications

Role of Muscle-Specific Histone Methyltransferase (Smyd1) in Exercise-Induced Cardioprotection against Pathological Remodeling after Myocardial Infarction

Role of Muscle-Specific Histone Methyltransferase (Smyd1) in Exercise-Induced Cardioprotection against Pathological Remodeling after Myocardial Infarction

Metformin: A Prospective Alternative for the Treatment of Chronic Pain

Single exercise stress reduces central neurotrophins levels and adenosine A₁ and A₂ receptors expression, but does not revert opioid‐induced hyperalgesia in rats

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AMPK contributes to aerobic exercise-induced antinociception downstream of endocannabinoids

Cited by 20 publications

References 39 publications

Role of Muscle-Specific Histone Methyltransferase (Smyd1) in Exercise-Induced Cardioprotection against Pathological Remodeling after Myocardial Infarction

Role of Muscle-Specific Histone Methyltransferase (Smyd1) in Exercise-Induced Cardioprotection against Pathological Remodeling after Myocardial Infarction

Metformin: A Prospective Alternative for the Treatment of Chronic Pain

Single exercise stress reduces central neurotrophins levels and adenosine A1 and A2 receptors expression, but does not revert opioid‐induced hyperalgesia in rats

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Single exercise stress reduces central neurotrophins levels and adenosine A₁ and A₂ receptors expression, but does not revert opioid‐induced hyperalgesia in rats