Catalase Enhances Viability of Human Chondrocytes in Culture by Reducing Reactive Oxygen Species and Counteracting Tumor Necrosis Factor-α-Induced Apoptosis

Abstract

Background/Aims: Both physiologic remodeling and pathologic regeneration of cartilage tissue rely upon chondrocyte functions and are benefited from factors that promote viability and inhibit apoptosis of the cell, and associated mechanisms. High level of reactive oxygen species (ROS) and proinflammatory cytokines activate apoptosis signaling and initiate cell death, which can be attenuated by antioxidants. This study examined the effect of catalase (CAT) on ROS and tumor necrosis factor-α (TNF-α)-induced apoptosis in human C28/I2 chondrocytes cultured in monolayer. Methods: Chondrocytes were treated with diluted CAT in the presence or absence of TNF-α and compared to untreated cells. Levels of hydrogen peroxide (H₂O₂) and mitochondrial membrane potential (Δψ_m) were measured using fluorescent labeling, cell apoptosis was assayed by flow cytometry using Annexin V/propidium iodide (PI) staining, gene expression was detected by quantitative real time polymerase chain reaction (qRT-PCR) and the proteins were investigated by Western blotting. Results: CAT effectively reduced the intracellular ROS caused by the monolayer culture system, enhanced the Δψ_m depending on the presence of TNF-α and promoted morphological features at sub-cellular level. CAT also attenuated the TNF-α-upregulated expression of factors/mediators of extrinsic cell death cascade and apoptotic caspases, ultimately resulted in promoted cellular viability. Conclusion: The anti-apoptotic effect of CAT on chondrocytes via scavenging ROS and suppressing TNF-α-induced cell apoptosis by TNF/TNF receptor (TNFR) mediated death signaling pathway and potentiate CAT as a complementary agent beneficial to cartilage remodeling and regeneration in vivo, and cell-based therapies of cartilage repair demanding viable cells expanded ex vivo.

PKR Promotes Oxidative Stress and Apoptosis of Human Articular Chondrocytes by Causing Mitochondrial Dysfunction through p38 MAPK Activation—PKR Activation Causes Apoptosis in Human Chondrocytes

“…Our results demonstrated consistent findings of mitochondrial dysfunction with reduced PGC-1α, decreased mitochondrial DNA copy number and mass in chondrocytes after TNF-α stimulation. In accordance with our findings, one of the previous studies has demonstrated that reduction of oxidative stress in chondrocytes counteracted the upregulated expression of apoptotic cascade factors caused by TNF-α [43], indicating oxidative stress as a key part to the TNF-α-induced apoptosis. The antioxidant deficiency has been revealed in OA chondrocytes with lower SOD activity and an increase of intracellular ROS production [44], and we proved that these changes might occur as a result of TNF-α activation.…”

Proximal Tubular Development Is Impaired with Downregulation of MAPK/ERK Signaling, HIF-1α, and Catalase by Hyperoxia Exposure in Neonatal Rats

“…Such translational/posttranslational inhibition may also induce the downregulation of catalase following neonatal hyperoxia in the current study. Since catalase enhances cell viability by reducing ROS-induced apoptosis [61], the hyperoxia-induced downregulation of catalase may cause tubular apoptosis, as we observed, and undermine proximal tubular development.…”

Reactive Oxygen Species-Induced Lipid Peroxidation in Apoptosis, Autophagy, and Ferroptosis

“…CAT can decompose the hydrogen peroxide into molecular oxygen and water. CAT significantly reduced oxidative stress and restored mitochondrial structure by enhancing the mitochondrial membrane potential ( Δψ m) so as to play an antiapoptotic effect and normalize replicative and wound healing capacity [13, 14]. Glutathione peroxidases (GPxs) consist of multiple isoenzymes with distinct subcellular locations exhibiting different tissue-specific expression patterns [15, 16].…”