Targeted deletion of ERK2 in cardiomyocytes attenuates hypertrophic response but provokes pathological stress induced cardiac dysfunction

Ulm, Susanne; Liu, Wei; Zi, Min; Tsui, Hoyee; Chowdhury, Sanjoy K.; Endo, Shogo; Satoh, Yasushi; Prehar, Sukhpal; Wang, Ruoxi; Cartwright, Elizabeth J.; Wang, Xin

doi:10.1016/j.yjmcc.2014.03.002

Cited by 33 publications

(31 citation statements)

References 44 publications

(45 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Depletion of ERK1/2 activity significantly decreased the severity of HF in TAC mice [18] . Over-expression of ERK1/2 promoted the compensated cardiac hypertrophy, although did not induce HF [19] .…”

Section: Discussionmentioning

confidence: 99%

Salvianolic Acid B Alleviates Heart Failure by Inactivating ERK1/2/GATA4 Signaling Pathway after Pressure Overload in Mice

Chen

Tan

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

BackgroundHeart failure(HF) is a dangerous disease that affects millions of patients. Radix Salvia is widely used in Chinese clinics to treat heart diseases. Salvianolic acid B(SalB) is the major active component of Radix Salvia. This study investigated the mechanisms of action and effects of SalB on HF in an experimental mouse model of HF.MethodsWe created a mouse model of HF by inducing pressure overload with transverse aortic constriction(TAC) surgery for 2 weeks and compared among 4 study groups: SHAM group (n = 10), TAC group (n = 9), TAC+MET group (metprolol, positive drug treatment, n = 9) and TAC+SalB group (SalB, 240 mg•kg-1•day-1, n = 9). Echocardiography was used to evaluate the dynamic changes in cardiac structure and function in vivo. Plasma brain natriuretic peptide (BNP) concentration was detected by Elisa method. In addition, H9C2 rat cardiomyocytes were cultured and Western blot were implemented to evaluate the phosphorylation of ERK1/2, AKT, and protein expression of GATA4.ResultsSalB significantly inhibited the phosphorylation of Thr202/Tyr204 sites of ERK1/2, but not Ser473 site of AKT, subsequently inhibited protein expression of GATA4 and plasma BNP(P < 0.001), and then inhibited HF at 2 weeks after TAC surgery.ConclusionsOur data provide a mechanism of inactivating the ERK1/2/GATA4 signaling pathway for SalB inhibition of the TAC-induced HF.

show abstract

Section: Discussionmentioning

confidence: 99%

Salvianolic Acid B Alleviates Heart Failure by Inactivating ERK1/2/GATA4 Signaling Pathway after Pressure Overload in Mice

Chen

Tan

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Previous studies demonstrated that cardiac hypertrophy is mediated by a PI3-K/AKT and ERK1/2 pathway, which can be pharmacological targets for cardioprotection [23, 24]. Considering there is still no effective Chinese medicine to treat cardiac hypertrophy, we did not set the positive control of Chinese medicine and different AT dosages.…”

Section: Discussionmentioning

confidence: 99%

Apocynum Tablet Protects against Cardiac Hypertrophy via Inhibiting AKT and ERK1/2 Phosphorylation after Pressure Overload

Liu

Gong

et al. 2014

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Background. Cardiac hypertrophy occurs in many cardiovascular diseases. Apocynum tablet (AT), a traditional Chinese medicine, has been widely used in China to treat patients with hypertension. However, the underlying molecular mechanisms of AT on the hypertension-induced cardiac hypertrophy remain elusive. The current study evaluated the effect and mechanisms of AT on cardiac hypertrophy. Methods. We created a mouse model of cardiac hypertrophy by inducing pressure overload with surgery of transverse aortic constriction (TAC) and then explored the effect of AT on the development of cardiac hypertrophy using 46 mice in 4 study groups (combinations of AT and TAC). In addition, we evaluated the signaling pathway of phosphorylation of ERK1/2, AKT, and protein expression of GATA4 in the cardioprotective effects of AT using Western blot. Results. AT inhibited the phosphorylation of Thr202/Tyr204 sites of ERK1/2, Ser473 site of AKT, and protein expression of GATA4 and significantly inhibited cardiac hypertrophy and cardiac fibrosis at 2 weeks after TAC surgery (P < 0.05). Conclusions. We experimentally demonstrated that AT inhibits cardiac hypertrophy via suppressing phosphorylation of ERK1/2 and AKT.

show abstract

“…These results demonstrated that ERK2 was responsible for cardiac hypertrophic growth. Knockout of ERK2 may play an essential role in treating pathological hypertrophic remodeling, despite inducing some apoptosis and cardiac dysfunction [83]. …”

Section: Inhibition Of Mek/erk To Study the Function Of Erkmentioning

confidence: 99%

The Role of ERK1/2 in the Development of Diabetic Cardiomyopathy

Sun

Tong

et al. 2016

IJMS

View full text Add to dashboard Cite

Diabetes mellitus is a chronic metabolic condition that affects carbohydrate, lipid and protein metabolism and may impair numerous organs and functions of the organism. Cardiac dysfunction afflicts many patients who experience the oxidative stress of the heart. Diabetic cardiomyopathy (DCM) is one of the major complications that accounts for more than half of diabetes-related morbidity and mortality cases. Chronic hyperglycemia and hyperlipidemia from diabetes mellitus cause cardiac oxidative stress, endothelial dysfunction, impaired cellular calcium handling, mitochondrial dysfunction, metabolic disturbances, and remodeling of the extracellular matrix, which ultimately lead to DCM. Although many studies have explored the mechanisms leading to DCM, the pathophysiology of DCM has not yet been fully clarified. In fact, as a potential mechanism, the associations between DCM development and mitogen-activated protein kinase (MAPK) activation have been the subjects of tremendous interest. Nonetheless, much remains to be investigated, such as tissue- and cell-specific processes of selection of MAPK activation between pro-apoptotic vs. pro-survival fate, as well as their relation with the pathogenesis of diabetes and associated complications. In general, it turns out that MAPK signaling pathways, such as extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK) and p38 MAP kinase, are demonstrated to be actively involved in myocardial dysfunction, hypertrophy, fibrosis and heart failure. As one of MAPK family members, the activation of ERK1/2 has also been known to be involved in cardiac hypertrophy and dysfunction. However, many recent studies have demonstrated that ERK1/2 signaling activation also plays a crucial role in FGF21 signaling and exerts a protective environment of glucose and lipid metabolism, therefore preventing abnormal healing and cardiac dysfunction. The duration, extent, and subcellular compartment of ERK1/2 activation are vital to differential biological effects of ERK1/2. Moreover, many intracellular events, including mitochondrial signaling and protein kinases, manipulate signaling upstream and downstream of MAPK, to influence myocardial survival or death. In this review, we will summarize the roles of ERK1/2 pathways in DCM development by the evidence from current studies and will present novel opinions on “differential influence of ERK1/2 action in cardiac dysfunction, and protection against myocardial ischemia-reperfusion injury”.

show abstract

Targeted deletion of ERK2 in cardiomyocytes attenuates hypertrophic response but provokes pathological stress induced cardiac dysfunction

Cited by 33 publications

References 44 publications

Salvianolic Acid B Alleviates Heart Failure by Inactivating ERK1/2/GATA4 Signaling Pathway after Pressure Overload in Mice

Salvianolic Acid B Alleviates Heart Failure by Inactivating ERK1/2/GATA4 Signaling Pathway after Pressure Overload in Mice

Apocynum Tablet Protects against Cardiac Hypertrophy via Inhibiting AKT and ERK1/2 Phosphorylation after Pressure Overload

The Role of ERK1/2 in the Development of Diabetic Cardiomyopathy

Contact Info

Product

Resources

About