Cardiac-specific overexpression of insulin-like growth factor II receptor-α interferes with the regulation of calcium homeostasis in the heart under hyperglycemic conditions

Lu, Shang-Yeh; Tsai, Bruce Chi‐Kang; Thao, Dao Van; Lai, Chin-Hu; Chen, Michael Yu‐Chih; Kuo, Wei‐Wen; Kuo, Chia‐Hua; Lin, Kuan-Ho; Hsieh, Dennis Jine‐Yuan; Huang, Chih‐Yang

doi:10.1007/s11033-023-08327-2

Cited by 3 publications

(1 citation statement)

References 45 publications

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“…The proteins were then transferred onto polyvinylidene difluoride membranes (Millipore, Bedford, MA, USA), which were incubated with 5% blocking buffer for 1 h. The membranes were incubated with primary antibodies (mTOR [#2983] and p53 [#2524] from Cell Signaling (Danvers, MA, USA), CHIP [sc-66830] and β-actin [sc-47778] from Santa Cruz Biotechnology, Santa Cruz,CA, USA) at 4° C overnight. Finally, the membranes were incubated with secondary antibodies (horseradish peroxidase-conjugated anti-rabbit and mouse (Santa Cruz Biotechnology, Santa Cruz, CA, USA) for 1 h at 25° C, and antibody binding was visualized using ECL western blotting luminal reagent (Santa Cruz Biotechnology) and the LAS-4000 mini (GE Healthcare Life Sciences) machine [34][35][36]. All chemicals were purchased from Sigma-Aldrich (St. Louis, MO, USA).…”

Section: Western Blot Analysismentioning

confidence: 99%

Human adipose-derived stem cells preconditioned with a novel herbal formulation Jing Shi attenuate doxorubicin-induced cardiac damage

Hsieh,

Tsai,

Barik

et al. 2023

Aging

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Pathological cardiac hypertrophy is a considerable contributor to global disease burden. Chinese herbal medicine (CHM) has been used to treat cardiovascular diseases since antiquity. Enhancing stem cell-mediated recovery through CHM represents a promising approach for protection against doxorubicin (Dox)-induced cardiac hypertrophy. Herein, we investigated whether human adipose-derived stem cells (hADSCs) preconditioned with novel herbal formulation Jing Si (JS) improved protective ability of stem cells against doxorubicin-induced cardiac damage. The effect of JS on hADSC viability and migration capacity was determined via MTT and migration assays, respectively. Co-culture of hADSC or JS-preconditioned hADSCs with H9c2 cells was analyzed with immunoblot, flow cytometry, TUNEL staining, LC3B staining, F-actin staining, and MitoSOX staining. The in vivo study was performed M-mode echocardiography after the treatment of JS and JS-preconditioned hADSCs by using Sprague Dawley (SD) rats. Our results indicated that JS at doses below 100 μg/mL had less cytotoxicity in hADSC and JS-preconditioned hADSCs exhibited better migration. Our results also revealed that DOX enhanced apoptosis, cardiac hypertrophy, and mitochondrial reactive oxygen species in DOX-challenged H9c2 cells, while H9c2 cells co-cultured with JS-preconditioned hADSCs alleviated these effects. It also enhanced the expression of autophagy marker LC3B, mTOR and CHIP in DOX-challenged H9c2 cells after co-culture with JS-preconditioned hADSCs. In Dox-challenged rats, the ejection fraction and fractional shortening improved in DOX-challenged SD rats exposed to JS-preconditioned hADSCs. Taken together, our data indicate that JS-preconditioned stem cells exhibit a cardioprotective capacity both in vitro and in vivo , highlighting the value of this therapeutic approach for regenerative therapy.

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Section: Western Blot Analysismentioning

confidence: 99%

Human adipose-derived stem cells preconditioned with a novel herbal formulation Jing Shi attenuate doxorubicin-induced cardiac damage

Hsieh,

Tsai,

Barik

et al. 2023

Aging

Self Cite

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Enhanced IGF‐IIRα Expression Exacerbates Lipopolysaccharide‐Induced Cardiac Inflammation, Hypertrophy, and Apoptosis Through Calcineurin Activation

Boonha,

Kuo,

Tsai

et al. 2024

Environmental Toxicology

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Cardiovascular disease is one of the leading causes of death worldwide and has a high prevalence. Insulin‐like growth factor‐II receptor α (IGF‐IIRα) acts as a stress‐inducible negative regulator. This study focused on the substantial impact of heightened expression of IGF‐IIRα in cardiac myoblasts and its association with the exacerbation of cardiac dysfunction. Using lipopolysaccharide (LPS)‐induced H9c2 cardiac myoblasts as a model for sepsis, we aimed to elucidate the molecular interactions between IGF‐IIRα and LPS in exacerbating cardiac injury. Our findings demonstrated a synergistic induction of cardiac inflammation and hypertrophy by LPS stimulation and IGF‐IIRα overexpression, leading to decreased cell survival. Excessive calcineurin activity, triggered by this combined condition, was identified as a key factor exacerbating the negative effects on cell survival. Cellular changes such as cell enlargement, disrupted actin filaments, and upregulation of hypertrophy‐related and inflammation‐related proteins contributed to the overall hypertrophic and inflammatory responses. Overexpression of IGF‐IIRα also exacerbated apoptosis induced by LPS in H9c2 cardiac myoblasts. Inhibiting calcineurin in LPS‐treated H9c2 cardiac myoblasts with IGF‐IIRα overexpression effectively reversed the detrimental effects, reducing cell damage and mitigating apoptosis‐related cardiac mechanisms. Our study suggests that under sepsis‐like conditions in the heart with IGF‐IIRα overexpression, hyperactivation of calcineurin worsens cardiac damage. Suppressing IGF‐IIRα and calcineurin expression could be a potential intervention to alleviate the impact of the illness and improve cardiac function.

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Folic Acid and Folinic Acid Protect Hearts of Aging Triple-transgenic Alzheimer’s Disease mice via IGF1R/PI3K/AKT and SIRT1/AMPK Pathways

Ju,

Huang,

Tsai

et al. 2023

Neurotox Res

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Cardiac-specific overexpression of insulin-like growth factor II receptor-α interferes with the regulation of calcium homeostasis in the heart under hyperglycemic conditions

Cited by 3 publications

References 45 publications

Human adipose-derived stem cells preconditioned with a novel herbal formulation Jing Shi attenuate doxorubicin-induced cardiac damage

Human adipose-derived stem cells preconditioned with a novel herbal formulation Jing Shi attenuate doxorubicin-induced cardiac damage

Enhanced IGF‐IIRα Expression Exacerbates Lipopolysaccharide‐Induced Cardiac Inflammation, Hypertrophy, and Apoptosis Through Calcineurin Activation

Folic Acid and Folinic Acid Protect Hearts of Aging Triple-transgenic Alzheimer’s Disease mice via IGF1R/PI3K/AKT and SIRT1/AMPK Pathways

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