Activation of protein kinase C‑α/heme oxygenase‑1 signaling pathway improves mitochondrial dynamics in lipopolysaccharide‑activated NR8383 cells

Abstract

Mitochondrial function and morphology are dynamically regulated by fusion and fission. Heme oxygenase-1 (HO-1), which may be upregulated by protein kinase C-α (PKC-α), improves mitochondrial dynamics by controlling the balance between fusion and fission and. However, whether the PKC-α/HO-1 signaling pathway is one of the underlying mechanisms in adjusting mitochondrial dynamics in lipopolysaccharide (LPS)-activated macrophages has remained elusive. To explore this, NR8383 cells were pre-treated with PKC-α inhibitor Go6976 or PKC-α activator phorbol-12-myristate-13-acetate for 30 min and then stimulated with LPS for 24 h. Next, the expression of PKC-α, HO-1, mitofusin 1 (Mfn1) and mitofusin 2 (Mfn2), optic atrophy 1 (OPA1), dynamin-related protein 1 (Drp1) and fission 1 (Fis1) was detected to evaluate the possible implication of the PKC-α/HO-1 signaling pathway in the LPS-induced NR8383 cells. The results indicated that activation of the PKC-α/HO-1 signaling pathway increased superoxide dismutase activities and the respiratory control ratio (RCR), decreased the levels of malondialdehyde, reactive oxygen species (ROS), Drp1 and Fis1, and simultaneously enhanced the levels of Mfn1, Mfn2 and OPA1. In contrast, the PKC-α inhibitor decreased the expression of RCR, Mfn1, Mfn2 and OPA1, and increased the expression of MDA and ROS in NR8383 cells. The results suggest that activation of the PKC-α/HO-1 signaling pathway is necessary for the balance of mitochondrial dynamics and oxidative stress in macrophages, which provides clues for probing novel strategies against the detrimental effects of sepsis and other disease states.

Transcutaneous Electrical Acupoint Stimulation Attenuates Lung Injury Caused by Tourniquet-induced Limb Ischemia/reperfusion During Lower Extremity Surgery: A Randomized Controlled Trial

“…Research shows that activation of PKC-a/HO-1 signaling pathway increases SOD activity and diminishes ROS content in LPS-activated alveolar macrophage cells [38]. Thus, the results in this study suggest that HO-1 is upregulated in lung injury and TEAS has a protective effect against I/R injury by possibly upregulating HO-1 expression.…”

Haemin pre‐treatment augments the cardiac protection of mesenchymal stem cells by inhibiting mitochondrial fission and improving survival

“…Furthermore, SD/H challenge up‐regulated the expression of p‐Drp1 ser616 and down‐regulated Mfn2, indicating SD/H induced mitochondrial fission. Recent studies have documented that HO‐1 plays an essential role in the regulation of mitochondrial fission . Haemin treatment significantly inhibited the ischaemia/reperfusion‐induced up‐regulation of Drp1 expression and enhanced the down‐regulation of Mfn2 in a mouse model of liver injury and thus attenuated hepatic injury.…”

Mevastatin-Induced AP-1-Dependent HO-1 Expression Suppresses Vascular Cell Adhesion Molecule-1 Expression and Monocyte Adhesion on Human Pulmonary Alveolar Epithelial Cells Challenged with TNF-α

“…Multiple isozymes of PKC can be categorized into three groups, including conventional (α, βI, βII, and γ), novel (β, ε, η, and θ), and atypical (ζ and ι) [42]. Among these isoforms, PKCα is one of the most prominent modulators of HO-1 expression, which improve mitochondrial dynamics via increasing the expression of fusion proteins [13]. The effect of PKCα was confirmed by our results indicating that MVS-induced HO-1 expression was mediated through PKCα membrane translocation and phosphorylation, which were inhibited by Gö6983 or transfection with its siRNA.…”

“…Protein kinase C (PKC)α is a member of the classical PKCs that takes a part in the regulation of cellular functions [12]. Upregulation of HO-1 via activation of PKCα could enhance fusion proteins and ameliorate mitochondrial injury [13]. Our previous report also indicated that rosiglitazone (a PPARγ agonist) increases HO-1 expression through the PKCα signaling pathway in HPAEpiCs [6].…”