Autophagy Plays a Protective Role in Advanced Glycation End Product-Induced Apoptosis in Cardiomyocytes

Hu, Pengfei; Zhou, Hui Ren; Lu, Ming; Dou, Liping; Bo, Gang; Wu, Jiale; Huang, Shouqiang

doi:10.1159/000430388

Cited by 26 publications

(16 citation statements)

References 32 publications

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“…There are many studies on AGEs and autophagy; RAGE enhances autophagy in pancreatic cancer, HUVECs, cardiomyocytes (Kang et al, 2011;Chen et al, 2015;Hu et al, 2015). However, there are also contradictory conclusions that AGE dose-dependently decreases mesangial cell and hFOB1.19 cell viability and induces apoptosis (Chang et al, 2013;Meng et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Effect of PPARG on AGEs‐induced AKT/MTOR signaling‐associated human chondrocytes autophagy

Wang

Zhang

Chen

et al. 2018

Cell Biology International

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Accumulation of advanced glycation end products (AGEs) in articular cartilage is thought to represent a major risk factor for osteoarthritis development. In this study we aimed to probe the role of AGEs in human chondrocytes and to determine the impact of the peroxisome proliferator-activated receptor-γ (PPARG) on AGEs-induced cell autophagy. Cell viability was measured after human chondrocytes were treated with different concentrations of AGEs with or without the PPARG inhibitor, T0070907, or agonist, pioglitazone. Autophagy activation markers (MAP2LC3, BECN1 and SQSTM1/P62), expression of PPARG and the phosphorylation levels of Akt/MTOR were determined by Western blotting; autophagosome formation was analyzed by transmission electron microscopy (TEM); autophagic flux was detected with mRFP-GFP-LC3 tandem construct. Low doses of AGEs over a short amount of time stimulated chondrocyte proliferation and autophagy by limiting phosphorylation of Akt/MTOR signaling. The addition of PPARG inhibitor T0070907 lead to defective autophagy. High dose and long exposure to AGEs inhibited cell viability and autophagy by increasing phosphorylation levels of Akt/MTOR signaling. The agonist, pioglitazone, was shown to protect cell autophagy in a dose-dependent manner. Our findings suggest AGEs can downregulate PPARG and that PPARG maintains cell viability by activating the Akt/MTOR signaling pathway as well as inducing chondrocyte autophagy.

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Section: Discussionmentioning

confidence: 99%

Effect of PPARG on AGEs‐induced AKT/MTOR signaling‐associated human chondrocytes autophagy

Wang

Zhang

Chen

et al. 2018

Cell Biology International

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“…Protein extraction and western blotting were performed as previously described [30]. In brief, 3×10 5 cells were seeded in 6-cm dishes and exposed to RA (0-6 μM) at different times.…”

Section: Protein Extraction and Western Blot Analysismentioning

confidence: 99%

Raddeanin a Suppresses Glioblastoma Growth by Inducing ROS Generation and Subsequent JNK Activation to Promote Cell Apoptosis

Peng

Wang

Shu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Raddeanin A (RA), an active pharmacological ingredient from Anemone raddeana Regel, plays an important role in tumor suppression. In this study, we assessed the potentially therapeutic effect of RA on glioblastoma and its underlying mechanisms. Methods: Cell viability was examined using the MTT assay. Invasive and migratory capacities were examined using Transwell and wound healing assays. Apoptosis was determined by Hoechst staining, flow cytometry, DCFH-fluorescent probe and immunohistochemical staining. Autophagy was detected by transmission electron microscopy and western blotting. A U251 glioma xenograft model was established to evaluate the effect of RA in vivo. Results: The data demonstrated that RA inhibited viability, and abrogated the invasive/migratory abilities of glioblastoma cells. In addition, RA induced apoptosis by reactive oxygen species (ROS)/ Jun N-terminal kinase (JNK) signaling in glioblastoma. Conversely, the antioxidant N-Acetyl-L-cysteine (NAC) and pan-caspase inhibitor z-VAD-fmk attenuated RA-induced apoptosis by scavenging ROS and inactivating caspase-3. Furthermore, the inhibition of autophagy by 3-MA exacerbated apoptosis through ROS generation and JNK phosphorylation. In vivo, RA exhibited a curative effect on U251-derived xenografts in nude mice. Conclusions: The results of this study suggest that RA suppressed the growth of glioblastoma, thus serving as a promising and potential strategy for glioblastoma chemotherapy.

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“…Well-established type 1 diabetic animal models, namely STZ-induced diabetic mice [9] and OVE26 mice [10], exhibit inhibited of cardiac autophagy along with cardiomyocyte apoptosis and cardiac dysfunction. The crosstalk between autophagy and apoptosis is complex, and Hu et al revealed that autophagy or autophagy-related proteins can lead to apoptosis or autophagic cell death under certain conditions [11]. …”

Section: Introductionmentioning

confidence: 99%

Exogenous H2S Protects Against Diabetic Cardiomyopathy by Activating Autophagy via the AMPK/mTOR Pathway

Yang

Zhang

Gao

et al. 2017

Cell Physiol Biochem

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Background/Aim: Autophagy plays an important role in cellular homeostasis through the disposal and recycling of cellular components. Hydrogen sulphide (H₂S) is the third endogenous gas that has been shown to confer cardiac protective effects. Given the regulation of autophagy in cardioprotection, this study aimed to investigate the protective effects of H₂S via autophagy during high glucose treatment. Methods: This study investigated the content of H₂S in the plasma as well as myocardial, ultrastructural changes in mitochondria and autophagosomes. This study also investigated the apoptotic rate using Hoechst/PI as well as expression of autophagy-associated proteins and mitochondrial apoptotic proteins in H9C2 cells treated with or without GYY4137. Mitochondria of cardiac tissues were isolated and RCR and ADP/O were also detected. AMPK knockdown was performed with siRNA transfection. Results: In a STZ-induced diabetic model, NaHS treatment not only increased the expression of p-AMPK in diabetic group but further activated cell autophagy. Following 48h high glucose, autophagosomes and cell viability were reduced. The present results showed that autophagy could be induced by H₂S, which was verified by autophagic ultrastructural observation and LC3-I/LC3-II conversion. In addition, the mitochondrial membrane potential (MMP) was significantly decreased. The expressions levels of autophagic-related proteins were significantly elevated. Moreover, H₂S activated the AMPK/rapamycin (mTOR) signalling pathway. Conclusions: Our findings demonstrated that H₂S decreases oxidative stress and protects against mitochondria injury, activates autophagy, and eventually leads to cardiac protection via the AMPK/mTOR pathway.

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Autophagy Plays a Protective Role in Advanced Glycation End Product-Induced Apoptosis in Cardiomyocytes

Cited by 26 publications

References 32 publications

Effect of PPARG on AGEs‐induced AKT/MTOR signaling‐associated human chondrocytes autophagy

Effect of PPARG on AGEs‐induced AKT/MTOR signaling‐associated human chondrocytes autophagy

Raddeanin a Suppresses Glioblastoma Growth by Inducing ROS Generation and Subsequent JNK Activation to Promote Cell Apoptosis

Exogenous H2S Protects Against Diabetic Cardiomyopathy by Activating Autophagy via the AMPK/mTOR Pathway

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