Tanshinone IIA and Cryptotanshinone Prevent Mitochondrial Dysfunction in Hypoxia-Induced H9c2 Cells: Association to Mitochondrial ROS, Intracellular Nitric Oxide, and Calcium Levels

Zhang

et al. 2017

Cell Physiol Biochem

Background/Aims: Myocardial infarction (MI) is a leading cause of morbidity and mortality. Here, we sought to explore the potential role and underlying mechanism of miR-145 in MI. Methods: H9c2 cells were cultured under persistent hypoxia to simulate MI. The hypoxia-induced injury was assessed on the basis of cell viability, migration, invasion and apoptosis. The expression of miR-145 was evaluated by qRT-PCR and the influence of aberrantly expressed miR-145 on H9c2 cells under hypoxia was also estimated. Utilizing bioinformatics methods, the target genes of miR-145 were verified by luciferase reporter assay. Then, effects of abnormally expressed target gene on miR-145 silenced H9c2 cells were assessed. Finally, the phosphorylation levels of key kinases in the phosphatidylinositol-3-kinase (PI3K)/AKT and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathways were detected by Western blot analysis. Results: Hypoxia remarkably lowered viability, migration and invasion but promoted cell apoptosis. Meantime, the miR-145 level was up-regulated in H9c2 cells under hypoxia. Following experiments suggested that hypoxia-induced injury was exacerbated by miR-145 overexpression while was alleviated by miR-145 silence. Rac1 was predicted and further validated to be a target gene of miR-145. The influence of miR-145 silencing on H9c2 cells under hypoxia could be reversed by down-regulation of Rac1. Additionally, the phosphorylation levels of PI3K, AKT, MAPK and ERK were all elevated in miR-145 silenced cells and these alterations were reversed by down-regulation of Rac1. Conclusion: miR-145 silencing could protect H9c2 cells against hypoxia-induced injury by targeting Rac1, in which PI3K/AKT and MAPK/ERK pathways might be involved.

Section: Discussionsupporting

confidence: 92%

MicroRNA-145 Aggravates Hypoxia-Induced Injury by Targeting Rac1 in H9c2 Cells

Zhang

et al. 2017

Cell Physiol Biochem

Biological & Pharmaceutical Bulletin

“…The level of aminotransferase, an important indicator of oxidative damage, is also increased in I/R injury. 25) Many studies have reported that CT is an antioxidant being effective to cardiovascular cell damage 11,26) and carbon tetrachlorideinduced hepatic injury. 27) Similarly, in our study, the SOD activities after applying CT, were dramatically higher compared with I/R group, but the MDA content and the aminotransferase activity significantly lower.…”

Section: Discussionmentioning

confidence: 99%

Cryptotanshinone Ameliorates Hepatic Normothermic Ischemia and Reperfusion Injury in Rats by Anti-mitochondrial Apoptosis

Sun

Yuan

et al. 2014

Cryptotanshinone (CT), isolated from the dried roots of Salvia militorrhiza, has been reported to have protective effects on myocardial and cerebral ischemia/reperfusion (I/R) injury both in vitro and in vivo. However, its effects and underlying mechanism on hepatic I/R injury remain unclear. To investigate its effects on hepatic I/R injury, thirty male Sprague-Dawley rats were randomized into 3 groups: a sham group, a vehicle-treated hepatic I/R group and a CT-treated (50 mg/kg) group. The hepatic I/R and CT-treated groups were subjected to 60 min of normothermic ischemia of the left lateral lobe of the liver, followed by 4 h of reperfusion. The animals were then sacrificed to collect the serum and the left liver lobe for assay. Hepatic function was protected, as evidenced by significantly reduced alanine aminotransferase (ALT), aspartate aminotransferase (AST) and malondialdehyde (MDA) levels in the CT-treated group as compared with I/R group. The terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) demonstrated significantly decreased apoptosis in the CT-administration animals. Western blotting demonstrated upregulation of the proapoptotic protein Bcl-2, as well as decreased levels of the activated form of caspase-3 and the cleaved form of its substrate, poly(ADP-ribose) polymerase (PARP) in the CT-treated group compared with those of the I/R group. In addition, the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (MAPKs) was inhibited by CT. Our data suggest that CT attenuates hepatic I/R injury by inhibiting the intrinsic pathway of apoptosis, mediated partly through the inhibition of JNK and p38 MAPK phosporylation.

Invest. Ophthalmol. Vis. Sci.

“…35,36 In another study, TanIIA protected H9c2 cells via preserving mitochondrial function by reducing the excess production of mitochondrial superoxide, superoxide dismutase activity, intracellular nitric oxide, and calcium levels, and restoring cellular ATP contents. 37 In brain microvascular endothelial cells, TanIIA suppressed the expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 by suppressing ROS production. 38 To gain further insight into the mechanism of TanIIA on ROS reduction, we next examined the effect of TanIIA on the expression of HO-1, an important cytoprotective, anti-inflammatory, and antioxidant enzyme.…”

Section: Discussionmentioning

confidence: 99%

“…However, recent studies have shown that solid dispersions of TanIIA with silica nanoparticles or low-molecular-weight chitosan achieved complete dissolution, increased the absorption rate, maintained drug stability, and showed improved oral bioavailability compared with TanIIA alone. 37,45 A study protocol for a randomized controlled trial has also been released to investigate the effect of sodium tanIIA sulfate and simvastatin on elevated serum levels of inflammatory markers in patients with coronary heart disease. 46 We believe the results in this study are noteworthy, as TanIIA can be used for the treatment of GO; further studies in humans using more developed types of TanIIA are needed to confirm these results.…”

Section: Discussionmentioning

confidence: 99%

Effect of Tanshinone IIA in an In Vitro Model of Graves' Orbitopathy

Rhiu

Chae

Lee³

et al. 2014

Our study results suggest that TanIIA possesses significant anti-inflammatory, antioxidant, and antiadipogenic effects in primary orbital fibroblasts. These results provide the basis for further study of the potential use of TanIIA to treat GO. Tanshinone IIA showed significant anti-inflammatory, antioxidant, and antiadipogenic effects in primary orbital fibroblasts from Graves' orbitopathy patients. These results provide the basis for further study of the potential use of tanshinone IIA to treat Graves' orbitopathy.