scholarly journals Activation of cAMP signaling transiently inhibits apoptosis in vascular smooth muscle cells in a site upstream of caspase-3

1999 ◽  
Vol 6 (7) ◽  
pp. 661-672 ◽  
Author(s):  
Sergei N Orlov ◽  
Nathalie Thorin-Trescases ◽  
Nickolai O Dulin ◽  
Than-Vinh Dam ◽  
Maria A Fortuno ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Caspase 3 ◽  
Muscle Cells ◽  
Camp Signaling ◽  
A Site

SET8，a novel regulator to ameliorate vascular calcification via activating PI3K/Akt mediated anti-apoptotic effects.

2021 ◽  
Author(s):  
Ya Ling Bai ◽  
Mei Juan Cheng ◽  
Jing Jing Jin ◽  
Hui Ran Zhang ◽  
Lei He ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Calcification ◽  
Vascular Smooth Muscle Cells ◽  
Caspase 3 ◽  
Muscle Cells ◽  
Akt Phosphorylation ◽  
High Phosphorus ◽  
Apoptotic Effects

Previous studies have showed that the apoptosis of vascular smooth muscle cells (VSMCs) underlies the mechanism of pathological calcifications in patients with chronic kidney disease (CKD). SET domain-containing protein 8 (SET8), as an efficient protein has been reported to modulate cell apoptosis in hepatocellular carcinoma cell, esophageal squamous cell and neuronal cell through regulating pathological processes, such as cell-cycle progression and transcription regulation. However, whether SET8 is involved in high phosphorus induced vascular calcification by mediating apoptosis remains undefined. Here, we reported that SET8 was located both in nucleus and cytoplasm, and significantly downregulated in calcification models. SET8 deficiency promoted the apoptosis of VSMCs, which was indicated by the increased Bax/Bcl-2 and cleaved caspase-3/total caspase-3 ratios. Mechanistically, PI3K/Akt pathway was mediated by SET8 and inhibition of PI3K/Akt signaling pathway by giving LY294002 or transfecting Akt phosphorylation inactivated mutation plasmid increased apoptosis and calcification. Akt phosphorylation constitutively activated mutation could reduce apoptosis and calcification of VSMCs. Furthermore, exogenous overexpression of SET8 could reverse the effect of PI3K/Akt inhibition on the apoptosis and calcification of VSMCs. In summary, our researches suggested that SET8 overexpression ameliorated high phosphorus induced calcification of vascular smooth muscle cells via activating PI3K/Akt mediated anti-apoptotic effects.

scholarly journals IGF-I but not insulin inhibits apoptosis at a low concentration in vascular smooth muscle cells

2003 ◽  
Vol 179 (2) ◽  
pp. 267-274 ◽  
Author(s):  
R Jamali ◽  
M Bao ◽  
HJ Arnqvist
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Caspase 3 ◽  
Chromatin Condensation ◽  
Muscle Cells ◽  
Serum Starvation ◽  
Maximal Effect ◽  
Igf I

Apoptosis of vascular smooth muscle cells (VSMCs) is of importance in the development of diabetic angiopathy. Our aim was to evaluate the effect of insulin and IGF-I on apoptosis in VSMCs. Rat aortic VSMCs were used and apoptosis was induced by serum starvation. As apoptotic markers we measured caspase-3 activity, histone-associated DNA fragments by ELISA and nuclear morphology by DAPI (4',6-diamidino-2-phenylindole) staining. Phosphorylation of IGF-I receptors was evaluated by Western blot. Serum starvation had increased caspase-3 activity even after 3 h. The highest activity was found after 3-12 h. IGF-I 10(-9 )M inhibited serum starvation-induced caspase-3 activity with a maximal effect after 12 h. When studied after starvation for 12 h, significant inhibitory effects on caspase-3 were found at IGF-I concentrations of 10(-8)-10(-7) M (P<0.01) and at an insulin concentration of 10(-6 )M (P<0.01). DNA fragmentation was detected by ELISA after 24 h and chromatin condensation and nuclear fragmentation by DAPI staining after 24 and 48 h respectively. IGF-I dose-dependently reduced apoptosis evaluated by ELISA, reaching a maximal effect at 10(-9) M. Insulin reduced apoptosis but the effect was weaker and a higher concentration was needed. IGF-I (10(-8 )M) and insulin at a very high concentration (10(-6) M) phosphorylated IGF-I receptors. Taken together, IGF-I and insulin have antiapoptotic effects on VSMCs but the effect of insulin is only found at high unphysiological concentration.

scholarly journals Melatonin Attenuates β-Glycerophosphate-Induced Calcification of Vascular Smooth Muscle Cells via a Wnt1/β-Catenin Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Wei Ren Chen ◽  
Yu Jie Zhou ◽  
Jia Qi Yang ◽  
Fang Liu ◽  
Ying Xin Zhao ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Signaling Pathway ◽  
Vascular Smooth Muscle Cells ◽  
Caspase 3 ◽  
Muscle Cells ◽  
Calcium Deposition ◽  
Western Blots ◽  
Alp Activity

Background. Melatonin has been demonstrated to protect against calcification in cyclosporine nephrotoxicity. The wingless-type MMTV integration site family member 1 (Wnt1)/β-catenin pathway is associated with cardiovascular calcification. This study aimed to explore whether melatonin could attenuate VSMC calcification through regulating the Wnt1/β-catenin signaling pathway. Methods. The effects of melatonin on vascular calcification were investigated in vascular smooth muscle cells (VSMCs). Calcium deposits were visualized by Alizarin Red Staining. Calcium content and alkaline phosphatase (ALP) activity were used to evaluate osteogenic differentiation. Western blots were used to measure the expression of runt-related transcription factor 2 (Runx2), α-smooth muscle actin (α-SMA), and cleaved caspase-3. Results. Melatonin markedly ameliorated calcium deposition and ALP activity. Runx2 and cleaved caspase-3 were found to be reduced and α-SMA was found to be increased by melatonin, together with a decrease in apoptosis. Immunofluorescence assay revealed a lower Runx2 protein level in the melatonin group. Melatonin treatment significantly decreased the expression of Wnt1 and β-catenin. Treatment with lithium chloride or transglutaminase 2 abrogated the protective effects of melatonin. Conclusion. Melatonin can attenuate β-GP-induced VSMC calcification through the suppression of Wnt1/β-catenin system.

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