COX6B1 relieves hypoxia/reoxygenation injury of neonatal rat cardiomyocytes by regulating mitochondrial function

Abstract

ObjectiveMitochondrial dysfunction plays a pivotal role in various pathophysiological processes of heart. Cytochrome oxidase subunit 6B1 (COX6B1) is a subunit of cytochrome oxidase.MethodsCardiomyocytes were isolated from neonatal SD rats (within 24 h of birth) by repeating digestion of collagenase and trypsin. COX6B1 over-expression and hypoxia/reoxygenation was conducted on neonatal rat cardiomyocytes. Cell viability, apoptosis rates, mitochondria membrane potential and mitochondrial permeabilization transition pores (mPTPs) were then determined respectively by Cell performing Counting Kit-8 (CCK-8), Annexin-V/PI assay, JC-1 assay, mPTP assay. The expression of cyto C and apoptosis-related factors were detected by RT-Qpcr and Western blot.ResultsHypoxia/reoxygenation increased apoptosis and mPTP levels, and decreased mitochondria membrane potential in I/R and I/R + EV groups. COX6B1 over-expression increased mitochondria cyto C, pro-caspase-3, pro-caspase-9 and bcl-2, while it decreased cytosol cyto C, cleaved-caspase-3, cleaved-caspase-9 and bax compared to I/R + EV group.ConclusionCOX6B1 protected cardiomyocytes from hypoxia/reoxygenation injury by reducing ROS production and cell apoptosis, during which reduction of the release of cytochrome C from mitochondria to cytosol was involved. Our study demonstrated that COX6B1 may be an candidate target gene in preventing hypoxia/reoxygenation injury of cardiomyocytes.

Xenon blunts NF-κB/NLRP3 inflammasome activation and improves acute onset of accelerated and severe lupus nephritis in mice

“…The proteomics analysis demonstrated that several molecular pathways associated with the inhibitory effects of Xe administration on NLRP3 inflammasome-mediated signaling and other inflammatory reactions may contribute to the mechanism of action of the potential renoprotective effects of Xe in the treated ASLN mice. Specifically, in the present study, we found an upregulated oxidative phosphorylation pathway, encoded by several genes, including COX6B1 38,50 , in the Xetreated ASLN mice. In this regard, COX6B1 is a subunit of cytochrome oxidase in mitochondria and plays a protective role in cardiomyocyte injury by reducing ROS production.…”

“…In this regard, COX6B1 is a subunit of cytochrome oxidase in mitochondria and plays a protective role in cardiomyocyte injury by reducing ROS production. 38 This finding further supports the likelihood that the therapeutic effects of Xe treatment involved inhibition of ROS production, although it is worth pursuing the exact role of COX6B1 and related molecular mechanisms in the LN mice.…”

“…Six upregulated and 48 downregulated pathways were observed in the XeþASLN mice, respectively (Figure 7c). Of those, the P2Y purigenic receptor signaling pathway, 37 IL-1b signaling, 14,20 and oxidative phosphorylation 38 have been implicated in NLRP3 inflammasome activation-related signaling. In addition to the preventive treatment with Xe in the ASLN mice, we further performed therapeutic approaches using a spontaneous LN model in NZB/W F1 (sLN) mice to mimic a clinical scenario.…”

Glioma cells are resistant to inflammation‑induced alterations of mitochondrial dynamics

“…As a cytochrome oxidase subunit, COX6B1 is encoded in the nuclear genome and serves critical roles in energy metabolism and regulation (50). It has been demonstrated that COX6B1 overexpression inhibits apoptosis and induces mitochondrial respiration and stress resistance (35,51). Accordingly, COX6B1 upregulation in glioma may be a response of the glioma cells to increase their resistance to a harsh environment.…”

Overexpression of COX6B1 protects against I/R‑induced neuronal injury in rat hippocampal neurons

“…COX6B1 protein may be associated with the development of the central nervous system (16). Previous studies reported that COX6B1 may protect the myocardium against I/R injury by regulating mitochondrial function (20,21); however, whether COX6B1 protects hippocampal neurons against I/R injury has not been reported, and the molecular mechanisms underlying the role of COX6B1 in the development of the nervous system remains unclear.…”