β-Adrenergic receptor stimulation induces endoplasmic reticulum stress in adult cardiac myocytes: role in apoptosis

Dalal, Suman; Foster, Cerrone R.; Das, Bhudev C.; Singh, Mahipal; Singh, Krishna

doi:10.1007/s11010-011-1205-7

Cited by 55 publications

(38 citation statements)

References 43 publications

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“…In our model, we cannot exclude that IH could directly induce apoptosis independently of ER stress, through the classical extrinsic or intrinsic mitochondrial apoptotic pathways. In fact, sympathetic activation and oxidative stress, both activated by IH, can also induce myocardial apoptosis, subsequent to ER stress activation or in an ER stress-independent manner (13,15,33,58,63).…”

Section: Chronic Exposure To Ih Promotes Cardiac Proapoptotic Er Stressmentioning

confidence: 99%

High-intensity training reduces intermittent hypoxia-induced ER stress and myocardial infarct size

Bourdier

Flore

Sanchez³

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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Chronic intermittent hypoxia (IH) is described as the major detrimental factor leading to cardiovascular morbimortality in obstructive sleep apnea (OSA) patients. OSA patients exhibit increased infarct size after a myocardial event, and previous animal studies have shown that chronic IH could be the main mechanism. Endoplasmic reticulum (ER) stress plays a major role in the pathophysiology of cardiovascular disease. High-intensity training (HIT) exerts beneficial effects on the cardiovascular system. Thus, we hypothesized that HIT could prevent IH-induced ER stress and the increase in infarct size. Male Wistar rats were exposed to 21 days of IH (21-5% fraction of inspired O2, 60-s cycle, 8 h/day) or normoxia. After 1 wk of IH alone, rats were submitted daily to both IH and HIT (2 ϫ 24 min, 15-30m/min). Rat hearts were either rapidly frozen to evaluate ER stress by Western blot analysis or submitted to an ischemia-reperfusion protocol ex vivo (30 min of global ischemia/ 120 min of reperfusion). IH induced cardiac proapoptotic ER stress, characterized by increased expression of glucose-regulated protein kinase 78, phosphorylated protein kinase-like ER kinase, activating transcription factor 4, and C/EBP homologous protein. IH-induced myocardial apoptosis was confirmed by increased expression of cleaved caspase-3. These IH-associated proapoptotic alterations were associated with a significant increase in infarct size (35.4 Ϯ 3.2% vs. 22.7 Ϯ 1.7% of ventricles in IH ϩ sedenary and normoxia ϩ sedentary groups, respectively, P Ͻ 0.05). HIT prevented both the IH-induced proapoptotic ER stress and increased myocardial infarct size (28.8 Ϯ 3.9% and 21.0 Ϯ 5.1% in IH ϩ HIT and normoxia ϩ HIT groups, respectively, P ϭ 0.28). In conclusion, these findings suggest that HIT could represent a preventive strategy to limit IHinduced myocardial ischemia-reperfusion damages in OSA patients.obstructive sleep apnea; intermittent hypoxia; ischemia-reperfusion; high-intensity aerobic training; endoplasmic reticulum stress NEW & NOTEWORTHYWe demonstrated that intermittent hypoxia induced cardiac proapoptotic ER stress and increased infarct size, which were prevented by high-intensity aerobic training. These results strengthen the need for early identification of patients with sleep apnea at risk for cardiovascular complications and suggest that exercise can be used as a new preventive strategy for these patients.

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Section: Chronic Exposure To Ih Promotes Cardiac Proapoptotic Er Stressmentioning

confidence: 99%

High-intensity training reduces intermittent hypoxia-induced ER stress and myocardial infarct size

Bourdier

Flore

Sanchez³

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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“…Even though we could measure a substantial decrease in Rhodopsin, the most abundant photoreceptor protein, in the treated BBS12-deperived photoreceptors, the maintained significant apoptotic activity indicated residual UPR activation. In an attempt to optimize our protective treatment, we tested a third pharmacological approach based on the UPR-specific Caspase12 inhibition (54,55). Used alone, the Caspase12 inhibitor INH was ϳ20% less efficient in preventing apoptosis than VPA or GBZ (Fig.…”

Section: Simultaneous Increase Of Er-resident Chaperone Bip Activitymentioning

confidence: 99%

Pharmacological Modulation of the Retinal Unfolded Protein Response in Bardet-Biedl Syndrome Reduces Apoptosis and Preserves Light Detection Ability

Mockel

Obringer

Hakvoort

et al. 2012

Journal of Biological Chemistry

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Background:Retinal degeneration is a main feature of Bardet-Biedl syndrome for which the mechanism causing photoreceptor cell apoptosis remains elusive. Results: Apoptosis is caused by protein accumulation in the photoreceptor inner segment activating an unfolded protein response. Conclusion: Pharmacological reduction of apoptosis preserves light detection ability. Significance: This therapeutic approach could be used to slow the degeneration and is potentially applicable to other ciliopathies.

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“…Salubrinal is a recently discovered selective inhibitor of the dephosphorylation of eukaryotic translation initiation factor 2α (eIF2α) (Boyce et al, 2005). It protects against endoplasmic reticulum-activated cell apoptosis or cardiomyocyte apoptosis (Dalal et al, 2012). Therefore, salubrinal could work as a new drug candidate for treating cardiac toxicity.…”

Section: Introductionmentioning

confidence: 99%

Role of salubrinal in protecting cardiomyocytes from doxorubicin-induced apoptosis

Gong¹,

Wu²,

Liang³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. We determined whether salubrinal can protect cardiomyocytes from doxorubicin-induced apoptosis and explored the related mechanisms to provide experimental evidence for exploring novel drug candidates to decrease cardiac toxicity. Neonatal rat cardiomyocytes were isolated, cultured in vitro, and pretreated with salubrinal (10, 20, or 40 μM) to observe their response to doxorubicin-induced cell apoptosis. Lactate dehydrogenase assay, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling staining, and flow cytometry were used to assess the extent of cardiomyocyte apoptosis. Fluorescent probes conjugated with 2',7'-dichlorofluorescein diacetate and a chemiluminescence assay were used to detect the production of reactive oxygen species. Western blotting was employed to quantify expression levels of cleaved caspase-3, cytosolic cytochrome c, and B-cell lymphoma-extra large (Bcl-xL). The mechanisms of salubrinal-related functions were also explored. Salubrinal effectively inhibited doxorubicin-induced reactive oxygen species production and N. Gong et al.

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β-Adrenergic receptor stimulation induces endoplasmic reticulum stress in adult cardiac myocytes: role in apoptosis

Cited by 55 publications

References 43 publications

High-intensity training reduces intermittent hypoxia-induced ER stress and myocardial infarct size

High-intensity training reduces intermittent hypoxia-induced ER stress and myocardial infarct size

Pharmacological Modulation of the Retinal Unfolded Protein Response in Bardet-Biedl Syndrome Reduces Apoptosis and Preserves Light Detection Ability

Role of salubrinal in protecting cardiomyocytes from doxorubicin-induced apoptosis

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