hCINAP serves a critical role in hypoxia‑induced cardiomyocyte apoptosis via modulating lactate production and mitochondrial‑mediated apoptosis signaling

Abstract

acute myocardial infarction (aMi) is a major cause of heart failure and is associated with insufficient myocardial oxygen supply. However, the molecular mechanisms underlying hypoxia-induced cardiomyocyte apoptosis are not completely understood. in the present study, the role of human coilin interacting nuclear aTPase protein (hcinaP) in cardiomyocytes was investigated. ac16 cells were divided into the following four groups: i) Small interfering (si) rna-control (ctrl); (ii) sirna-hcinaP; (iii) empty vector; and (iv) hcinaP-Flag. Protein expression was assessed using western blotting. MTT and apoptosis assays were conducted to detect cell viability and apoptosis, respectively. ccK8 assays and apoptosis assays were used to detect cell viability and apoptosis, respectively. hcinaP promoter activity was examined by luciferase reporter assay. hcinaP expression was induced in a hypoxia-inducible factor-1α-dependent manner under hypoxic conditions. compared with the sirna-ctrl group, hcinaP knockdown inhibited apoptosis, whereas compared with the vector group, hcinaP overexpression increased apoptosis under hypoxic conditions. Mechanistically, compared with the sirna-ctrl group, hcinaP knockdown decreased hypoxia-induced lactate accumulation via regulating lactate dehydrogenase a activity. Moreover, the results indicated that hcinaP was associated with mitochondrial-mediated apoptosis via caspase signaling. collectively, the present study suggested that hcinaP was an important regulator in hypoxia-induced apoptosis and may serve as a promising therapeutic target for aMi.

FAT10 Combined with Miltefosine Inhibits Mitochondrial Apoptosis and Energy Metabolism in Hypoxia-Induced H9C2 Cells by Regulating the PI3K/AKT Signaling Pathway

“…Under OS conditions, MFN2 expression declines, whereas the protein related to mitochondrial fission, DRP1, elevates, leading to mitochondrial fragmentation, decreased energy metabolism, and ultimately mitochondrial apoptosis [ 31 – 33 ]. Our results indicated that hypoxia enhanced OS response, promoted mitochondrial apoptosis, and inhibited the metabolism of mitochondrial energy in H9C2 cells; these findings conform to those of previous studies [ 34 – 37 ]. However, the effects of hypoxia were weakened by the FAT10 overexpression.…”

Hypoxia‐induced miR‐182‐5p regulates vascular smooth muscle cell phenotypic switch by targeting RGS5

“…Lysis buffer (Solarbio) was used to extract the protein from cells, followed by quantifying the protein content using a BCA protein quantitative kit (Beyotime Institute of Biotechnology, China). Western blots were performed according to standard procedures as previously described (Xie et al, 2021). Primary antibodies used in this study: anti‐actin (AC026; ABclonal), anti‐α‐SMA (19245; Cell Signaling), anti‐SMARCC1 (ab172638; Abcam), anti‐cytokeratin 8 (CK‐8) (ab53280; Abcam), anti‐cytokeratin 18 (CK‐18) (ab53280; Abcam), anti‐P‐MYPT (3040; Cell Signaling), anti‐MYPT (2634; Cell Signaling), anti‐RGS5 (NBP2‐249454; Novus Biologicals), anti‐SMMHC (A4064; ABclonal), anti‐RhoA (ab86297; Abcam).…”

Unique structural features of the adenylate kinase hCINAP/AK6 and its multifaceted functions in carcinogenesis and tumor progression

“…Two recent studies showed that cervical cancer cells exposed to hypoxia accumulated hCINAP in a HIF-1αdependent manner. Under hypoxic conditions, hCINAP both promotes epithelial-to-mesenchymal transition (EMT) by enhancing Akt/mTOR signaling and inhibits hypoxia-induced apoptosis [49,50]. hCINAP knockdown decreases hypoxia-induced lactate accumulation via regulated LDHA activity.…”