Endoplasmic Reticulum-Mitochondria Contacts: A Potential Therapy Target for Cardiovascular Remodeling-Associated Diseases

Wang, Yu; Zhang, Xinrong; Wen, Ya; Li, Sixuan; Lü, Xiaohui; Xu, Ran; Li, Chao

doi:10.3389/fcell.2021.774989

Cited by 17 publications

(12 citation statements)

References 281 publications

(337 reference statements)

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“…Next, we studied the mechanism by which LBP protects skin cells against PM2.5-induced apoptosis and cytotoxicity. The ER is the main place for protein processing and folding in the cell, and it is the largest Ca 2+ storage organelle in the cell [ 36 ]. When cells are stressed by external factors, the ER stress response will be activated, which may cause Ca 2+ imbalance [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Lycium Barbarum polysaccharide protects HaCaT cells from PM2.5-induced apoptosis via inhibiting oxidative stress, ER stress and autophagy

Zhu

Bingrong

et al. 2022

Redox Report

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Objectives: Lycium barbarum polysaccharide (LBP) is a natural polysaccharide extracted from Lycium barbarum that has anti-inflammatory, anti-apoptotic and anti-aging effects, and plays a role in the prevention and treatment of various diseases. In this study, we investigated the therapeutic effect of LBP on particulate matter 2.5 (PM2.5)-induced skin damage. Methods: Cell viability was analyzed by MTT and LDH assays. Apoptosis was analyzed by Annexin V-FITC/PI staining. Oxidative stress/damage were assessed by intracellular ROS levels, MDA content and SOD activity. The intracellular protein expression was analyzed by Western blot. Mitochondrial damage was assayed by mitochondrial membrane potential with JC-1 probe. LC3-GFP adenovirus was transfected into HaCaT cells to analyze intracellular autophagosome levels. Results: In PM2.5-treated HaCaT cells, LBP pretreatment reduced PM2.5-induced cytotoxicity, ameliorated cell morphology and reduced cell apoptosis. LBP also inhibited the expression levels of GRP78 and CHOP, reduced the conversion of LC3I to LC3II, inhibited Bax protein and activated Bcl-2 protein. Furthermore, LBP inhibited PM2.5-induced mitochondrial autophagy (mitophagy) and mitochondrial damage. PM2.5-induced autophagy was regulated by endoplasmic reticulum (ER) stress. Conclusion: LBP protects skin cells from PM2.5-induced cytotoxicity by regulating the oxidative stress-ER stress-autophagy-apoptosis signaling axis, revealing that LBP has a great potential for the skin protection.

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Section: Discussionmentioning

confidence: 99%

Lycium Barbarum polysaccharide protects HaCaT cells from PM2.5-induced apoptosis via inhibiting oxidative stress, ER stress and autophagy

Zhu

Bingrong

et al. 2022

Redox Report

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“…Cytosolic overload has been previously associated with an increase in Na + /Ca 2+ exchanger (NCX1) expression, which is encoded by HIF-1 [ 59 ] and known to predispose to ROS-mediated myocardial injury [ 60 ]. Finally, cytosolic Ca 2+ overloading contributes to Serca2a activation by phospholamban phosphorylation that could explain Ca 2+ rapid accumulation in ER and subsequent ER stress [ 61 ]. Otherwise, it has been demonstrated that HIF-1α overexpression promotes PLB phosphorylation and alters Ca 2+ handling [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Intermittent Hypoxia-Induced Cardiomyocyte Death Is Mediated by HIF-1 Dependent MAM Disruption

et al. 2022

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Rationale: Intermittent hypoxia (IH) is one of the main features of sleep-disordered breathing (SDB). Recent findings indicate that hypoxia inducible factor-1 (HIF-1) promotes cardiomyocytes apoptosis during chronic IH, but the mechanisms involved remain to be elucidated. Here, we hypothesize that IH-induced ER stress is associated with mitochondria-associated ER membrane (MAM) alteration and mitochondrial dysfunction, through HIF-1 activation. Methods: Right atrial appendage biopsies from patients with and without SDB were used to determine HIF-1α, Grp78 and CHOP expressions. Wild-type and HIF-1α+/− mice were exposed to normoxia (N) or IH (21–5% O2, 60 cycles/h, 8 h/day) for 21 days. Expressions of HIF-1α, Grp78 and CHOP, and apoptosis, were measured by Western blot and immunochemistry. In isolated cardiomyocytes, we examined structural integrity of MAM by proximity ligation assay and their function by measuring ER-to-mitochondria Ca2+ transfer by confocal microscopy. Finally, we measured mitochondrial respiration using oxygraphy and calcium retention capacity (CRC) by spectrofluorometry. MAM structure was also investigated in H9C2 cells incubated with 1 mM CoCl2, a potent HIF-1α inducer. Results: In human atrial biopsies and mice, IH induced HIF-1 activation, ER stress and apoptosis. IH disrupted MAM, altered Ca2+ homeostasis, mitochondrial respiration and CRC. Importantly, IH had no effect in HIF-1α+/− mice. Similar to what observed under IH, HIF-1α overexpression was associated with MAM alteration in H9C2. Conclusion: IH-induced ER stress, MAM alterations and mitochondrial dysfunction were mediated by HIF-1; all these intermediate mechanisms ultimately inducing cardiomyocyte apoptosis. This suggests that HIF-1 modulation might limit the deleterious cardiac effects of SDB.

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“…After an index event, misfolded proteins are accumulated in the ER promoting the activation of the unfolded protein response in order to maintain proteostasis. In the case of failure of the misfolded protein repair, or of a large amount of accumulated unfolded proteins, a vicious circle begins [ 62 , 63 ]. This vicious circle is characterized by the loss of homeostatic capacity, promoting apoptosis.…”

Section: Inflammationmentioning

confidence: 99%

Inflammation and Heart Failure: Searching for the Enemy—Reaching the Entelechy

Paraskevaidis

Farmakis

Papingiotis

et al. 2023

JCDD

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The pivotal role of inflammation in the pathophysiology of heart-failure (HF) development and progression has long been recognized. High blood levels of pro-inflammatory and inflammatory markers are present and associated with adverse outcomes in patients with HF. In addition, there seems to be an interrelation between inflammation and neurohormonal activation, the cornerstone of HF pathophysiology and management. However, clinical trials involving anti-inflammatory agents have shown inconclusive or even contradictory results in improving HF outcomes. In the present review, we try to shed some light on the reciprocal relationship between inflammation and HF in an attempt to identify the central regulating factors, such as inflammatory cells and soluble mediators and the related inflammatory pathways as potential therapeutic targets.

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Endoplasmic Reticulum-Mitochondria Contacts: A Potential Therapy Target for Cardiovascular Remodeling-Associated Diseases

Cited by 17 publications

References 281 publications

Lycium Barbarum polysaccharide protects HaCaT cells from PM2.5-induced apoptosis via inhibiting oxidative stress, ER stress and autophagy

Lycium Barbarum polysaccharide protects HaCaT cells from PM2.5-induced apoptosis via inhibiting oxidative stress, ER stress and autophagy

Intermittent Hypoxia-Induced Cardiomyocyte Death Is Mediated by HIF-1 Dependent MAM Disruption

Inflammation and Heart Failure: Searching for the Enemy—Reaching the Entelechy

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