scholarly journals Mitochondrial fission is required for cardiomyocyte hypertrophy mediated by a Ca2+-calcineurin signaling pathway

2014 ◽  
Vol 127 (12) ◽  
pp. 2659-2671 ◽  
Author(s):  
C. Pennanen ◽  
V. Parra ◽  
C. Lopez-Crisosto ◽  
P. E. Morales ◽  
A. del Campo ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Mitochondrial Fission ◽  
Cardiomyocyte Hypertrophy ◽  
Calcineurin Signaling

scholarly journals High glucose induces Drp1-mediated mitochondrial fission via the Orai1 calcium channel to participate in diabetic cardiomyocyte hypertrophy

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Qing-Rui Wu ◽  
Dan-Lin Zheng ◽  
Pei-Ming Liu ◽  
Hui Yang ◽  
Lu-An Li ◽  
...  
Keyword(s):  
Calcium Channel ◽  
Mitochondrial Dysfunction ◽  
High Glucose ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Calcium Handling ◽  
Cardiomyocyte Hypertrophy ◽  
Mitochondrial Morphology ◽  
Calmodulin Binding ◽  
Downstream Target

AbstractMitochondrial dysfunction and impaired Ca2+ handling are involved in the development of diabetic cardiomyopathy (DCM). Dynamic relative protein 1 (Drp1) regulates mitochondrial fission by changing its level of phosphorylation, and the Orai1 (Ca2+ release-activated calcium channel protein 1) calcium channel is important for the increase in Ca2+ entry into cardiomyocytes. We aimed to explore the mechanism of Drp1 and Orai1 in cardiomyocyte hypertrophy caused by high glucose (HG). We found that Zucker diabetic fat rats induced by administration of a high-fat diet develop cardiac hypertrophy and impaired cardiac function, accompanied by the activation of mitochondrial dynamics and calcium handling pathway-related proteins. Moreover, HG induces cardiomyocyte hypertrophy, accompanied by abnormal mitochondrial morphology and function, and increased Orai1-mediated Ca2+ influx. Mechanistically, the Drp1 inhibitor mitochondrial division inhibitor 1 (Mdivi-1) prevents cardiomyocyte hypertrophy induced by HG by reducing phosphorylation of Drp1 at serine 616 (S616) and increasing phosphorylation at S637. Inhibition of Orai1 with single guide RNA (sgOrai1) or an inhibitor (BTP2) not only suppressed Drp1 activity and calmodulin-binding catalytic subunit A (CnA) and phosphorylated-extracellular signal-regulated kinase (p-ERK1/2) expression but also alleviated mitochondrial dysfunction and cardiomyocyte hypertrophy caused by HG. In addition, the CnA inhibitor cyclosporin A and p-ERK1/2 inhibitor U0126 improved HG-induced cardiomyocyte hypertrophy by promoting and inhibiting phosphorylation of Drp1 at S637 and S616, respectively. In summary, we identified Drp1 as a downstream target of Orai1-mediated Ca2+ entry, via activation by p-ERK1/2-mediated phosphorylation at S616 or CnA-mediated dephosphorylation at S637 in DCM. Thus, the Orai1–Drp1 axis is a novel target for treating DCM.

Leptin-induced cardiomyocyte hypertrophy is associated with enhanced mitochondrial fission

2018 ◽  
Vol 454 (1-2) ◽  
pp. 33-44 ◽  
Author(s):  
Chian Ju Jong ◽  
Justin Yeung ◽  
Emily Tseung ◽  
Morris Karmazyn
Keyword(s):  
Mitochondrial Fission ◽  
Cardiomyocyte Hypertrophy

Melatonin attenuates angiotensin II-induced cardiomyocyte hypertrophy through the CyPA/CD147 signaling pathway

2016 ◽  
Vol 422 (1-2) ◽  
pp. 85-95 ◽  
Author(s):  
Hongyan Su ◽  
Jingyuan Li ◽  
Tongshuai Chen ◽  
Na Li ◽  
Jie Xiao ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Signaling Pathway ◽  
Cardiomyocyte Hypertrophy

Odanacatib Inhibits Resistin-induced Cardiomyocyte Hypertrophy Through the Inactivation of ERK Signaling Pathway

2017 ◽  
Vol 13 (2) ◽  
pp. 212-217
Author(s):  
Xian Zheng ◽  
Guanchang Cheng ◽  
Jianwei Luo ◽  
Qunhui Ye ◽  
Yongzhi Deng ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Erk Signaling ◽  
Cardiomyocyte Hypertrophy

scholarly journals Role of Retrograde Trafficking in Stress Response, Host Cell Interactions, and Virulence of Candida albicans

2013 ◽  
Vol 13 (2) ◽  
pp. 279-287 ◽  
Author(s):  
Yaoping Liu ◽  
Norma V. Solis ◽  
Clemens J. Heilmann ◽  
Quynh T. Phan ◽  
Aaron P. Mitchell ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Host Cell ◽  
Signaling Pathway ◽  
Stress Resistance ◽  
Cell Interactions ◽  
Content Type ◽  
Retrograde Trafficking ◽  
Host Cell Interactions ◽  
Vacuolar Protein ◽  
Calcineurin Signaling

ABSTRACTInSaccharomyces cerevisiae, the vacuolar protein sorting complexes Vps51/52/53/54 and Vps15/30/34/38 are essential for efficient endosome-to-Golgi complex retrograde transport. Here we investigated the function of Vps15 and Vps51, representative members of these complexes, in the stress resistance, host cell interactions, and virulence ofCandida albicans. We found thatC. albicansvps15Δ/Δ andvps51Δ/Δ mutants had abnormal vacuolar morphology, impaired retrograde protein trafficking, and dramatically increased susceptibility to a variety of stressors. These mutants also had reduced capacity to invade and damage oral epithelial cellsin vitroand attenuated virulence in the mouse model of oropharyngeal candidiasis. Proteomic analysis of the cell wall of thevps51Δ/Δ mutant revealed increased levels of the Crh11 and Utr2 transglycosylases, which are targets of the calcineurin signaling pathway. The transcript levels of the calcineurin pathway membersCHR11,UTR2,CRZ1,CNA1, andCNA2were elevated in thevps15Δ/Δ andvps51Δ/Δ mutants. Furthermore, these strains were highly sensitive to the calcineurin-specific inhibitor FK506. Also, deletion ofCHR11andUTR2further increased the stress susceptibility of these mutants. In contrast, overexpression ofCRH11andUTR2partially rescued their defects in stress resistance, but not host cell interactions. Therefore, intact retrograde trafficking inC. albicansis essential for stress resistance, host cell interactions, and virulence. Aberrant retrograde trafficking stimulates the calcineurin signaling pathway, leading to the increased expression of Chr11 and Utr2, which enablesC. albicansto withstand environmental stress.

scholarly journals FGF21 Mediates Mesenchymal Stem Cell Senescence via Regulation of Mitochondrial Dynamics

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Xin Li ◽  
Yimei Hong ◽  
Haiwei He ◽  
Guojun Jiang ◽  
Wei You ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Signaling Pathway ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Mitochondrial Fusion ◽  
Fibroblast Growth Factor 21 ◽  
Early Passage ◽  
Ampk Signaling ◽  
Novel Strategy

Mesenchymal stem cell- (MSC-) based therapy is a novel strategy in regenerative medicine. The functional and regenerative capacities of MSCs decline with senescence. Nonetheless, the potential mechanisms that underlie their senescence are not fully understood. This study was aimed at exploring the potential mechanisms of fibroblast growth factor 21 (FGF21) in the regulation of MSC senescence. The senescence of MSCs was determined by senescence-associated β-galactosidase (SA-β-gal) staining. The morphology and the level of mitochondrial reactive oxygen species (ROS) of MSCs were assessed by MitoTracker and Mito-Sox staining, respectively. The expression of FGF21 and mitochondrial dynamics-related proteins was detected by Western blotting. As MSCs were expanded in vitro, the expression of FGF21 decreased. Depletion of FGF21 enhanced production of mitochondrial reactive oxidative species (ROS) and increased the senescence of early-passage MSCs whereas inhibition of ROS abolished these effects. The senescent MSCs exhibited increased mitochondrial fusion and decreased mitochondrial fission. Treatment of early-passage MSCs with FGF21 siRNA enhanced mitochondrial fusion and reduced mitochondrial fission. Moreover, treatment of mitofusin2- (Mfn2-) siRNA inhibited depletion of FGF21-induced MSC senescence. Furthermore, we demonstrated that depletion of FGF21-induced mitochondrial fusion was regulated by the AMPK signaling pathway. Treatment with an AMPK activator, AICAR, abrogated the depletion of FGF21-induced senescence of MSCs by inhibiting mitochondrial fusion. Compared with MSCs isolated from young donors, those derived from aged donors showed a lower level of FGF21 and a higher level of senescent activity. Furthermore, overexpression of FGF21 in aged MSCs inhibited senescence. Our study shows that FGF21, via the AMPK signaling pathway, regulates the senescence of MSCs by mediating mitochondrial dynamics. Targeting FGF21 might represent a novel strategy to improve the quality and quantity of MSCs.

scholarly journals Aspirin Attenuates Angiotensin II-induced Cardiomyocyte Hypertrophy by Inhibiting the Ca2+/Calcineurin-NFAT Signaling Pathway

2016 ◽  
Vol 34 (1) ◽  
pp. 21-29 ◽  
Author(s):  
Zheyu Yin ◽  
Xiaoyun Wang ◽  
Lan Zhang ◽  
Hongfeng Zhou ◽  
Li Wei ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Signaling Pathway ◽  
Cardiomyocyte Hypertrophy
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