The molecular regulation of GADD153 in apoptosis of cultured vascular smooth muscle cells by cyclic mechanical stretch

Cheng, Wan-Jung; Hung, Huei Fong; Wang, Bao Wei; Shyu, Kou Gi

doi:10.1093/cvr/cvm057

Cited by 51 publications

(46 citation statements)

References 34 publications

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“…These data are congruent with previous studies showing that palmitate is a potent inducer of ER stress [38] . Recent evidence shows that atherosclerosis is associated with ER dysfunction and the accumulation of unfolded proteins [39][40][41][42][43] . Suppressing ER-stress signaling significantly attenuates accelerated atherogenesis [40] .…”

Section: Discussionmentioning

confidence: 99%

Wogonin ameliorates lipotoxicity-induced apoptosis of cultured vascular smooth muscle cells via interfering with DAG-PKC pathway

et al. 2011

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Aim: To investigate the effects of wogonin (5,7-dihydroxy-8-methoxyflavone) extracted from Scutellaria baicalensis Georgi (S baicalensis) on lipotoxicity-induced apoptosis of vascular smooth muscle cells (VSMCs) and the underlying mechanisms. Methods: Cultured VSMCs were used. Apoptosis of VSMCs was induced by palmitate (0.75 mmol/L), and detected using TUNEL assay. The expression levels of protein and phosphorylated protein were measured using Western blot analysis. Results: Treatment of VSMCs with wogonin (10, 25 and 50 µmol/L) significantly attenuated the apoptosis and endoplasmic reticulum (ER) stress induced by palmitate in concentration-and time-dependent manners. Wogonin (50 µmol/L) decreased palmitate-induced reactive oxygen species (ROS) generation. The ER stress inhibitor 4-phenyl butyric acid (5 mmol/L) significantly decreased palmitateinduced apoptotic cells, and occluded the anti-apoptotic effect of wogonin (25 µmol/L). Wogonin (10, 25 and 50 µmol/L) significantly reduced the intracellular diacylglycerol (DAG) accumulation and expression levels of phosphorylated PKCs in palmitate-treated VSMCs. Conclusion: Our results suggest that wogonin inhibits lipotoxicity-induced apoptosis of VSMCs via suppressing the intracellular DAG accumulation and subsequent inhibition of PKC phosphorylation. Wogonin has therapeutic potential for the prevention and treatment of atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Wogonin ameliorates lipotoxicity-induced apoptosis of cultured vascular smooth muscle cells via interfering with DAG-PKC pathway

et al. 2011

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“…Western blot was performed as described previously (12). Proteins of interest were revealed with specific antibodies, including Klf4 and myocardin, as indicated (1:200 dilution) for 1 h at room temperature followed by incubation with a 1:5000 dilution of horseradish peroxidase-conjugated polyclonal antirabbit antibody for 1 h at room temperature.…”

Section: Western Blot Analysismentioning

confidence: 99%

“…The real-time polymerase chain reaction (PCR) was performed as described previously (12). The primers used were as follows: Klf4, 5′-ATGCAGGCTG GGCAAAAC-3′ (forward) and 5′-CAGCC GTCCCAGTCACAGT-3′ (reverse); myocardin, 5′-CAGCTGGCTAACCAA GGCTT-3′ (forward) and 5′-TCAGA GAGTCTTCAGTCTTGGCACTA-3′; GAPDH, 5′-CATCACCATCTTCCA GGAGC-3′ (forward) and 5′-GGATG ATGTTCTGGGCTGCC-3′ (reverse).…”

Section: Real-time Polymerase Chain Reactionmentioning

confidence: 99%

Angiotensin II Downregulates MicroRNA-145 to Regulate Kruppel-like Factor 4 and Myocardin Expression in Human Coronary Arterial Smooth Muscle Cells under High Glucose Conditions

Shyu

Cheng²,

Wang³

2015

Mol Med

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MicroRNA (miR)-145 is the most abundant miR in vascular smooth muscle cells (VSMCs). However, the effect of hyperglycemia on the regulation of miR-145 is unknown. We hypothesized that the hyperglycemic condition activates a proinflammatory response that mediates the expression of miR-145 in VSMCs. We investigated whether miR-145 serves as a critical regulator to regulate the downstream proliferation factors (including Kruppel-like factor 4 [Klf4] and myocardin) in VSMCs under hyperglycemic conditions. Human coronary artery smooth muscle cells (HCASMCs) were cultured under high glucose conditions. Sustained high glucose at 25 mmol/L significantly decreased the expression of miR-145 in HCASMCs. High glucose significantly increased angiotensin II (Ang II) secretion from HCASMCs and Ang II suppressed miR-145 expression in HCASMCs. Ang II repression of miR145 expression resulted in increased Klf4 and decreased myocardin expression under conditions of high glucose. Overexpression of miR-145 significantly decreased Klf4 and increased myocardin expression and inhibited HCASMC proliferation and migration induced by a high glucose state. Balloon injury of the carotid artery in diabetic rats was performed to investigate miR-145, Klf and myocardin expression. The expression of miR-145 was maximally increased at 7 d after carotid injury and gradually declined thereafter. Overexpression of miR-145 and treatment with valsartan reversed Klf4 and myocardin protein expression induced by balloon injury and improved vascular injury. In conclusion, our study reveals that Ang II downregulates miR-145 to regulate Klf4 and myocardin expression in HCASMCs under high glucose conditions. Ang II plays a critical role in the regulation of miR-145 under hyperglycemic conditions.

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“…Indeed, (1) cyclic stretch enhances GADD153 expression in cultured rat vascular smooth muscle cells, 39 (2) mechanical stress regulates GADD153 expression in cardiomyocytes, 40 (3) neonatal cardiomyocytes subjected to hypoxia-reperfusion or an in vivo IR insult to the heart causes marked increase in GADD153 expression, 41 and (4) deficiency of GADD153 reduces myocardial IR injury. 15 As expected, pressure overload was associated with marked expression of GADD153 in the ischemic-reperfused heart.…”

Section: 35mentioning

confidence: 99%

Pressure Overload Regulates Expression of Cytokines, γH2AX, and Growth Arrest- and DNA-Damage Inducible Protein 153 via Glycogen Synthase Kinase-3β in Ischemic-Reperfused Hearts

2013

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Abstract-The growth arrest-and DNA-damage inducible protein 153 (GADD153) regulates both apoptosis and inflammatory response. Importantly, glycogen synthase kinase-3β (GSK-3β) may provide a mechanistic link for cellular expression of GADD153, inflammatory response, and cell death. We previously showed that pressure overload exacerbates myocardial ischemia reperfusion injury associated with significant reduction in phosphorylated (inactive) GSK-3β. This raises the possibility that pressure overload, through a GSK-3β-dependent mechanism, increases GADD153 expression, thereby upregulating inflammatory cytokine production and contributing to worsening of myocardial ischemia reperfusion injury. Accordingly, Langendorff-perfused rat hearts were subjected to global ischemia reperfusion protocol in the absence or presence of the GSK-3β inhibitor, lithium chloride (1 mmol/L), with perfusion pressure set at 80 or 160 cmH 2 O; normoxic hearts served as controls. Compared with normoxia, an ischemia reperfusion insult increased expressions of proinflammatory cytokines, γH2AX, and GADD153 in association with increased cell death. In the ischemic-reperfused hearts, pressure overload did the following: (1) reduced interleukin-10 but increased interleukin-17 (cardiomyocytes), without affecting interleukin-23; (2) increased expressions of γH2AX and GADD153; (3) decreased 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) aggregates but increased JC-1 monomers (suggestive of reduced mitochondrial membrane potential, ψ m ); and (4) increased annexin V immunostaining as well as apoptotic and necrotic cell death. Treatment with lithium chloride caused a robust increase in interleukin-10, preserved ψ m , and markedly decreased all other parameters with the effect being most prominent for hearts perfused at the high pressure.In conclusion, pressure overload, via a GSK-3β-dependent mechanism, exacerbates cell death in the isolated ischemicreperfused heart involving regulation of inflammatory response, DNA injury, and GADD153 expression.

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The molecular regulation of GADD153 in apoptosis of cultured vascular smooth muscle cells by cyclic mechanical stretch

Abstract: Cyclic stretch enhanced GADD153 expression in cultured rat VSMCs. The stretch-induced GADD153 is mediated by TNF-alpha, at least in part, through the JNK and AP-1 pathway. These findings suggest that GADD153 plays a role in stretch-induced VSMC apoptosis.

Cited by 51 publications

References 34 publications

Wogonin ameliorates lipotoxicity-induced apoptosis of cultured vascular smooth muscle cells via interfering with DAG-PKC pathway

Wogonin ameliorates lipotoxicity-induced apoptosis of cultured vascular smooth muscle cells via interfering with DAG-PKC pathway

Angiotensin II Downregulates MicroRNA-145 to Regulate Kruppel-like Factor 4 and Myocardin Expression in Human Coronary Arterial Smooth Muscle Cells under High Glucose Conditions

Pressure Overload Regulates Expression of Cytokines, γH2AX, and Growth Arrest- and DNA-Damage Inducible Protein 153 via Glycogen Synthase Kinase-3β in Ischemic-Reperfused Hearts

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