Nutritional preconditioning induced by astragaloside Ⅳ on isolated hearts and cardiomyocytes against myocardial ischemia injury via improving Bcl-2-mediated mitochondrial function

Luo, Yong; Wan, Qin; Xu, Min; Zhou, Qing; Chen, Xuepiao; Yin, Dong; He, Huan; He, Ming

doi:10.1016/j.cbi.2019.06.036

Cited by 31 publications

(31 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…14-3-3 is the molecular target of many active ingredients of plants. We have confirmed that 14-3-3 assists PKCε, Bcl-2, and other functional proteins to locate to mitochondria and protect cardiomyocytes and vascular endothelial cells against multiple injuries [7,9,[40][41][42][43]. Further studies are needed to define specific mechanism(s) of action for Cap-activated 14-3-3η in anoxia and A/R injured cardiomyocytes.…”

Section: Discussionsupporting

confidence: 53%

Capsaicin Alleviates the Deteriorative Mitochondrial Function by Upregulating 14-3-3η in Anoxic or Anoxic/Reoxygenated Cardiomyocytes

Qiao

Yang

et al. 2020

Oxidative Medicine and Cellular Longevity

Self Cite

View full text Add to dashboard Cite

Reactive oxygen species (ROS) are byproducts of a defective electron transport chain (ETC). The redox couples, GSH/GSSG and NAD+/NADH, play an essential role in physiology as internal defenses against excessive ROS generation by facilitating intracellular/mitochondrial (mt) redox homeostasis. Anoxia alone and anoxia/reoxygenation (A/R) are dissimilar pathological processes. In this study, we measured the impact of capsaicin (Cap) on these pathological processes using a primary cultured neonatal rat cardiomyocyte in vitro model. The results showed that overproduction of ROS was tightly associated with disturbed GSH/GSSG and NAD+/NADH suppressed mt complex I and III activities, decreased oxygen consumption rates, and elevated extracellular acidification rates. During anoxia or A/R period, these indices interact with each other causing the mitochondrial function to worsen. Cap protected cardiomyocytes against the different stages of A/R injury by rescuing NAD+/NADH, GSH/GSSG, and mt complex I/III activities and cellular energy metabolism. Importantly, Cap-mediated upregulation of 14-3-3η, a protective phosphoserine-binding protein in cardiomyocytes, ameliorated mt function caused by a disruptive redox status and an impaired ETC. In conclusion, redox pair, mt complex I/III, and metabolic equilibrium were significantly different in anoxia alone and A/R injury; Cap through upregulating 14-3-3η plays a protection against the above injury in cardiomyocyte.

show abstract

Section: Discussionsupporting

confidence: 53%

Capsaicin Alleviates the Deteriorative Mitochondrial Function by Upregulating 14-3-3η in Anoxic or Anoxic/Reoxygenated Cardiomyocytes

Qiao

Yang

et al. 2020

Oxidative Medicine and Cellular Longevity

Self Cite

View full text Add to dashboard Cite

show abstract

“…Bcl‐2 and Bax play a very important role in apoptosis (Korsmeyer, Shutter, Veis, Merry, & Oltvai, ) and also are critical in regulating the effects of mitochondrial membrane permeability (Wang et al, ) and mitochondrial respiratory chain function (Luo et al, ). A study showed that AS‐IV upregulated Bcl‐2 expression in cardiomyocytes (Luo et al, ). The caspases are known to act downstream of Bax/Bcl‐2 and play key roles in the execution of apoptosis (Salakou et al, ).…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV reverses simvastatin‐induced skeletal muscle injury by activating the AMPK‐PGC‐1α signalling pathway

Jiang

Yang

Dang

et al. 2019

Phytotherapy Research

View full text Add to dashboard Cite

In this study, we investigated the effect of astragaloside IV on skeletal muscle energy metabolism disorder caused by statins and explored the possible mechanisms. Highfat diet-fed apolipoprotein E knockout (ApoE −/− ) mice performed aerobic exercise and were administered simvastatin, simvastatin + trimetazidine, or simvastatin + astragaloside IV by gavage. At the end of treatment, exercise performance was assessed by the hanging grid test, forelimb grip test, and running tolerance test.Moreover, plasma lipid and creatine kinase concentrations were measured. After sacrifice, the gastrocnemius muscle was used to assess muscle morphology, and energy metabolism was evaluated by determining the concentration of lactic acid and the storage capacity of adenosine triphosphate and glycogen. Mitochondrial function was assessed by measuring mitochondrial complex III and citrate synthase activity and membrane potential. In addition, oxidative stress was assessed by determining the level of hydrogen peroxide. Finally, using western blotting and reverse transcription polymerase chain reaction, we explored the mechanism of astragaloside IV in alleviating simvastatin-induced muscle injury. Our results demonstrated that astragaloside IV reversed simvastatin-induced muscle injury without affecting the lipid-lowering effect of simvastatin. Moreover, astragaloside IV promoted the phosphorylation of AMPK and activated PGC-1α, which upregulated the expression of NRF1 to enhance energy metabolism and inhibit skeletal muscle cell apoptosis. K E Y W O R D Sastragaloside IV, energy metabolism, mitochondria, simvastatin, skeletal muscle injury

show abstract

“…Mitochondria are multifunctional organelles and can actively or passively drive cellular dysfunction or demise [54, 55]. Certainly, the structural and functional integrity is fundamental to cellular life.…”

Section: Discussionmentioning

confidence: 99%

Iron Overload Damages the Endothelial Mitochondria via the ROS/ADMA/DDAHII/eNOS/NO Pathway

Qiao

Zhou

et al. 2019

Oxidative Medicine and Cellular Longevity

Self Cite

View full text Add to dashboard Cite

It has been recognized that iron overload may harm the body's health. Vascular endothelial cells (VECs) are one of the main targets of iron overload injury, and the mechanism involved was thought to be related to the excessive generation of reactive oxygen species (ROS). However, the subcellular and temporal characteristics of ROS generation, potential downstream mechanisms, and target organelles in VECs injured by iron overload have not been expounded yet. In this study, we elucidated the abovementioned issues through both in vivo and in vitro experiments. Mice were fed pellet diets that were supplemented with iron for 4 consecutive months. Results showed that the thoracic aortic strips' endothelium-dependent dilation was significantly impaired and associated with inflammatory changes, noticeable under brown TUNEL-positive staining in microscopy analysis. In addition, the serum content of asymmetric dimethylarginine (ADMA) increased, whereas nitric oxide (NO) levels decreased. Furthermore, the dimethylarginine dimethylaminohydrolase II (DDAHII) expression and activity, as well as the phosphorylation of endothelial nitric oxide synthase (eNOS) in aortic tissue, were inhibited. Human umbilical vein endothelial cells were treated with 50 μM iron dextran for 48 hours, after which the cell viability, NO content, DDAHII expression and activity, and phosphorylation of eNOS decreased and lactate dehydrogenase and caspase-3 activity, ADMA content, and apoptotic cells significantly increased. After the addition of L-arginine (L-Arg) or pAD/DDAHII, the abovementioned changes were reversed. By dynamically detecting the changes of ROS generation in the cytoplasm and mitochondria and interfering with different aspects of signaling pathways, we have confirmed for the first time that excessive ROS originates from the cytoplasm and activates the ROS-induced ROS release (RIRR) mechanism, leading to mitochondrial dysfunction. Together, our data suggested that excessive free iron ions produced excess ROS in the cytoplasm. Thus, excess ROS create one vicious circle by activating the ADMA/eNOS/DDAHII/NO pathway and another vicious circle by activation of the RIRR mechanism, which, when combined, induce a ROS burst, resulting in mitochondrial dysfunction and damaged VECs.

show abstract

Nutritional preconditioning induced by astragaloside Ⅳ on isolated hearts and cardiomyocytes against myocardial ischemia injury via improving Bcl-2-mediated mitochondrial function

Cited by 31 publications

References 48 publications

Capsaicin Alleviates the Deteriorative Mitochondrial Function by Upregulating 14-3-3η in Anoxic or Anoxic/Reoxygenated Cardiomyocytes

Capsaicin Alleviates the Deteriorative Mitochondrial Function by Upregulating 14-3-3η in Anoxic or Anoxic/Reoxygenated Cardiomyocytes

Astragaloside IV reverses simvastatin‐induced skeletal muscle injury by activating the AMPK‐PGC‐1α signalling pathway

Iron Overload Damages the Endothelial Mitochondria via the ROS/ADMA/DDAHII/eNOS/NO Pathway

Contact Info

Product

Resources

About