Intermedin protects thapsigargin‑induced endoplasmic reticulum stress in cardiomyocytes by modulating protein kinase A and sarco/endoplasmic reticulum Ca²⁺‑ATPase

Abstract

Intermedin (IMD) is a calcitonin/calcitonin-related peptide that elicits cardioprotective effects in a variety of heart diseases, such as cardiac hypertrophy and heart failure. However, the molecular mechanism of IMD remains unclear. The present study investigated the effects of IMD on neonatal rat ventricular myocytes treated with thapsigargin. The results of the present study demonstrated that thapsigargin induced apoptosis in cardiomyocytes in a dose-and time-dependent manner. Thapsigargin induced endoplasmic reticulum stress, as determined by increased expression levels of 78-kDa glucose-regulated protein, C/EBP-homologous protein and caspase-12, which were dose-dependently attenuated by pretreatment with IMD. In addition, IMD treatment counteracted the thapsigargin-induced suppression of sarco/endoplasmic reticulum Ca 2+-ATPase (SERCA) activity and protein expression levels, and cytoplasmic Ca 2+ overload. IMD treatment also augmented the phosphorylation of phospholamban, which is a crucial regulator of SERCA. Additionally, treatment with the protein kinase A antagonist H-89 inhibited the IMD-mediated cardioprotective effects, including SERCA activity restoration, anti-Ca 2+ overload, endoplasmic reticulum stress inhibition and antiapoptosis effects. In conclusion, the results of the present study suggested that IMD may protect cardiomyocytes against thapsigargin-induced endoplasmic reticulum stress and the associated apoptosis at least partly by activating the protein kinase A/SERCA pathway.

Protective effect of naringin against radiation‐induced heart disease in rats via Sirt1/NF‐κB signaling pathway and endoplasmic reticulum stress

“…Persistent or excessive endoplasmic reticulum (ER) stress can stimulate cardiomyocyte apoptosis, which is also one of the key mechanisms of cardiomyocyte injury (Fa et al., 2022; Li, Guo, et al., 2021; Zhang et al., 2020). To explore whether XR irradiation could regulate ER stress in rat heart tissue, the expression levels of ER stress marker proteins GRP78, CHOP, ATF6, and caspase 12 in rat heart were detected after different doses of XR irradiation.…”

Pharmacokinetics and antioxidant activity of dihydrocaffeic acid grafted chitosan nanomicelles loaded with chicoric acid in broilers

“…Chloroquine stabilizes lysosomal membranes, reducing lysosomal enzyme release and hindering lysosomal activity ( Fedele and Proud, 2020 ). Monensin disrupts Golgi transport to the cell membrane by interfering with the Golgi apparatus ( Zhu et al, 2020 ), whereas thapsigargin inhibits endoplasmic reticulum Ca2+-ATPase, impeding endoplasmic reticulum transport ( Li et al, 2021 ). From the intracellular results, it's evident that microtubules play a significant role throughout CA's intracellular process.…”

Taurine attenuates ER stress‑associated apoptosis and catabolism in nucleus pulposus cells

“…in present study, TG was chosen to assess the extent to which er stress associates with the cytoprotective effects of taurine in nP cells. TG can be extracted from the plant Thapsia garganica and is a classical inhibitor of er ca 2+ aTPase (53). er ca 2+ aTPase dysfunction has been demonstrated to serve a role in various diseases, including idd (54).…”