Inhibition of ERK-Drp1 signaling and mitochondria fragmentation alleviates IGF-IIR-induced mitochondria dysfunction during heart failure

Huang, Chih‐Yang; Lai, Chao-Hung; Kuo, Chia‐Hua; Chiang, Shu‐Fen; Pai, Peiying; Lin, Jing‐Ying; Chang, Chih-Fen; Viswanadha, Vijaya Padma; Kuo, Wei‐Wen

doi:10.1016/j.yjmcc.2018.08.006

Cited by 54 publications

(31 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The AMP-activated protein kinase (AMPK) and extracellular signal-regulated kinase (ERK) pathways are important kinases for the phosphorylation of Drp1 at S637 and S616, respectively [ 39 – 42 ]. In our study, acrolein (100 μmol/L) significantly decreased p-AMPK while increasing p-ERK in a time-dependent manner (Fig.…”

Section: Resultsmentioning

confidence: 99%

Acrolein Aggravates Secondary Brain Injury After Intracerebral Hemorrhage Through Drp1-Mediated Mitochondrial Oxidative Damage in Mice

Cui

Guo

et al. 2020

Neurosci. Bull.

View full text Add to dashboard Cite

Clinical advances in the treatment of intracranial hemorrhage (ICH) are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury. Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases. Our results indicated a significant increase in the level of acrolein after ICH in mouse brain. In primary neurons, acrolein induced an increase in mitochondrial fragmentation, loss of mitochondrial membrane potential, generation of reactive oxidative species, and release of mitochondrial cytochrome c. Mechanistically, acrolein facilitated the translocation of dynamin-related protein1 (Drp1) from the cytoplasm onto the mitochondrial membrane and led to excessive mitochondrial fission. Further studies found that treatment with hydralazine (an acrolein scavenger) significantly reversed Drp1 translocation and the morphological damage of mitochondria after ICH. In parallel, the neural apoptosis, brain edema, and neurological functional deficits induced by ICH were also remarkably alleviated. In conclusion, our results identify acrolein as an important contributor to the secondary brain injury following ICH. Meanwhile, we uncovered a novel mechanism by which Drp1-mediated mitochondrial oxidative damage is involved in acrolein-induced brain injury.

show abstract

Section: Resultsmentioning

confidence: 99%

Acrolein Aggravates Secondary Brain Injury After Intracerebral Hemorrhage Through Drp1-Mediated Mitochondrial Oxidative Damage in Mice

Cui

Guo

et al. 2020

Neurosci. Bull.

View full text Add to dashboard Cite

show abstract

“…In particular, overactivation of JNK in vivo can cause restrictive cardiomyopathy and cardiac fibrosis, as well as leading to conduction defects and heart failure [48][49][50]. JNK is also considered an essential modulator for mitochondrial homeostasis and apoptosis in the onset and progression of heart failure [47,51,52]. Activation of JNK/p38 cascades has been demonstrated to aggravate the development of MI/R injury [53].…”

Section: Discussionmentioning

confidence: 99%

Melatonin Ameliorates MI-Induced Cardiac Remodeling and Apoptosis through a JNK/p53-Dependent Mechanism in Diabetes Mellitus

Sun

et al. 2020

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Diabetes mellitus, a worldwide health threat, is considered an independent risk factor for cardiovascular diseases. The overall cardiovascular risk of diabetes is similar to the one having one myocardial infarction (MI) attack although the precise impact of diabetes on MI-induced myocardial anomalies remains elusive. Given that mortality following MI is much greater in diabetic patients compared to nondiabetic patients, this study was designed to examine the effect of melatonin on MI injury-induced myocardial dysfunction in diabetes. Adult mice were made diabetic using high-fat feeding and streptozotocin (100 mg/kg body weight) prior to MI and were treated with melatonin (50 mg/kg/d, p.o.) for 4 weeks prior to assessment of cardiac geometry and function. The MI procedure in diabetes displayed overt changes in cardiac geometry (chamber dilation and interstitial fibrosis) and functional anomalies (reduced fractional shortening and cardiomyocyte contractile capacity) in association with elevated c-Jun N-terminal kinase (JNK) phosphorylation and p53 level. Melatonin treatment markedly attenuated cardiac dysfunction and myocardial fibrosis in post-MI diabetic mice. Furthermore, melatonin decreased JNK phosphorylation, reduced p53 levels, and suppressed apoptosis in hearts from the post-MI diabetic group. In vitro findings revealed that melatonin effectively counteracted high-glucose/high fat-hypoxia-induced cardiomyocyte apoptosis and contractile dysfunction through a JNK-mediated mechanism, the effects of which were impaired by the JNK activator anisomycin. In summary, our study suggests that melatonin protects against myocardial injury in post-MI mice with diabetes, which offers a new therapeutic strategy for the management of MI-induced cardiac injury in diabetes.

show abstract

“…Interestingly, in rectal cancer, the JNK pathway modifies the activity of DRP1 by inducing the posttranscriptional phosphorylation of DRP1 at Ser616 (Li et al 2017). Notably, in heart failure, the JNK pathway also affects DRP1 expression through the ERK signaling pathway (Huang et al 2018). In the present study, we found that the JNK pathway is activated by the LPS-induced inflammation microenvironment and that increased JNK expression is followed by DRP1 upregulation, which indicated that the JNK pathway could be considered the upstream mediator of DRP1.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, several researchers have shown that mitochondrial malfunction occurs before the myocardial inflammatory response and cardiomyocyte death (Davidson et al 2018;Kamura et al 2018). Several mechanisms have been proposed to explain sepsis-mediated cardiomyocyte mitochondrial death in septic cardiomyopathy, and these include mitochondrial respiratory disorder, calcium overload, mitochondrial autophagy arrest, and mitochondrial membrane damage (Deussen 2018;Huang et al 2018). Mitochondrial fission has recently been recognized as an upstream signal for mitochondrial homeostasis .…”

Section: Introductionmentioning

confidence: 99%

Irisin ameliorates septic cardiomyopathy via inhibiting DRP1-related mitochondrial fission and normalizing the JNK-LATS2 signaling pathway

Tan

Ouyang

Xiao

et al. 2019

Cell Stress and Chaperones

View full text Add to dashboard Cite

Irisin plays a protective effect in acute and chronic myocardial damage, but its role in septic cardiomyopathy is unclear. The aim of our study was to explore the in vivo and in vitro effects of irisin using an LPS-induced septic cardiomyopathy model. Our results demonstrated that irisin treatment attenuated LPS-mediated cardiomyocyte death and myocardial dysfunction. At the molecular level, LPS application was associated with mitochondrial oxidative injury, cardiomyocyte ATP depletion and caspaserelated apoptosis activation. In contrast, the irisin treatment sustained mitochondrial function by inhibiting DRP1-related mitochondrial fission and the reactivation of mitochondrial fission impaired the protective action of irisin on inflammation-attacked mitochondria and cardiomyocytes. Additionally, we found that irisin modulated DRP1-related mitochondrial fission through the JNK-LATS2 signaling pathway. JNK activation and/or LATS2 overexpression abolished the beneficial effects of irisin on LPSmediated mitochondrial stress and cardiomyocyte death. Altogether, our results illustrate that LPS-mediated activation of DRP1related mitochondrial fission through the JNK-LATS2 pathway participates in the pathogenesis of septic cardiomyopathy. Irisin could be used in the future as an effective therapy for sepsis-induced myocardial depression because it corrects DRP1-related mitochondrial fission and normalizes the JNK-LATS2 signaling pathway.

show abstract

Inhibition of ERK-Drp1 signaling and mitochondria fragmentation alleviates IGF-IIR-induced mitochondria dysfunction during heart failure

Cited by 54 publications

References 47 publications

Acrolein Aggravates Secondary Brain Injury After Intracerebral Hemorrhage Through Drp1-Mediated Mitochondrial Oxidative Damage in Mice

Acrolein Aggravates Secondary Brain Injury After Intracerebral Hemorrhage Through Drp1-Mediated Mitochondrial Oxidative Damage in Mice

Melatonin Ameliorates MI-Induced Cardiac Remodeling and Apoptosis through a JNK/p53-Dependent Mechanism in Diabetes Mellitus

Irisin ameliorates septic cardiomyopathy via inhibiting DRP1-related mitochondrial fission and normalizing the JNK-LATS2 signaling pathway

Contact Info

Product

Resources

About