Cytoprotective role of humanin in lens epithelial cell oxidative stress‑induced injury

Abstract

oxidative stress-induced injury and apoptosis of human lens epithelial cells (Hlecs) are early events in the development of age-related cataracts (arcs). Humanin (Hn) is a mitochondrial-related peptide that serves a cytoprotective role in various cell types and animal models. Following Hn knockdown or overexpression, the level of reactive oxygen species (roS), mitochondrial membrane potential and mitochondrial dna copy number, cell viability, ldH activity and apoptosis of Hlecs under oxidative stress were detected, and apoptosis and autophagy were detected via transmission electron microscopy. The results suggested that Hn may be involved in the response of Hlecs to oxidative stress, and that HN expression was significantly upregulated under oxidative stress conditions. Furthermore, exogenous Hn reduced intracellular roS content and mitochondrial damage, and enhanced mitochondrial biosynthesis; however, this protection was lost in an endogenous Hn knockdown cell model. in addition, to the best of our knowledge, the present study was the first to identify that Hn increased mitochondrial autophagy, which was involved in reducing roS production under oxidative stress. The present study indicated a potential mechanism underlying the anti-oxidative damage and apoptotic effects of Hn under oxidative stress. in conclusion, Hn may be a potential therapeutic target for ARCs as it has a significant cellular protective effect on Hlecs under oxidative stress; therefore, further study is required to investigate its role in the occurrence and development of arcs.

The role of oxidative stress in intervertebral disc cellular senescence

“…Humanin (HN), a mitochondria-related peptide translated by the open reading frame of mitochondrial 16S rRNA, plays a role in resisting cellular oxidative damage and inhibiting apoptosis in response to oxidative stress. Experimentally, exogenous HN was shown to reduce intracellular ROS content and the extent of cellular damage and to enhance cellular anabolism and mitochondrial function; this anti-oxidative effect was lost in a cellular model in which HN expression was inhibited ( 137 ).In treating age-related cataracts and macular degeneration, HN exerts a positive antioxidant effect. In oxidatively stressed human lens epithelial cells (HLECs) and retinal pigment epithelial cells (hRPE): HN protects cells by upregulating GSH expression levels in mitochondria, thereby resisting the impairment of mitochondrial function by oxidative stress and activating caspase 3 and caspase 4 expression ( 138 , 139 ).…”

The Role of Mitochondria-Derived Peptides in Cardiovascular Diseases and Their Potential as Therapeutic Targets

“…Protection from OS and ER stress: Mitochondria are the main energy-producing organelles, but also the main ROS producer, which causes oxidative damage to proteins, lipids and mtDNA, and is involved in the development of low-grade chronic inflammation, ageing, CVD and premature death [68,69]. However, experiments on several cell lines (such as retinal pigment epithelium, lens epithelial cells, cortical neurons and neuroblastoma cancer cells) proved that HN could protect mitochondria and cells from oxidative stress and ER stress [70][71][72][73]. HN acts via a mitochondrial antioxidant defence system, where HN stimulates expression of SOD1 (Superoxide Dismutase 1), biosynthesis and restoring the mitochondrial pool of glutathione [72,74].…”

Reactive Oxygen Species and Eye Aging in Cataracts through Biomolecular Mechanisms

“…Recent immunochemistry works light up new pathways and processes that in the nearly past years were just lucubrated. This is the case of Rho-associated kinase (ROCK) built by protein serine, threonine kinase, a family of protein kinase (PKA, PKG, PKC), with 2 domains, important both for regulating adhesion and apoptosis under stress habits; furthermore p53 also known as the guardian of the genome, with particularly sense of notifying damage in DNA, has a protective response all around cell metabolism, this two associations ROCK1 and p53 coexist in the cytoplasm and both expressions expand by H202 and moreover ROCK1 mediated p53 phosphorylation upregulation exactly at serine 15 level, made this relevant because of the cooperation between ROCK1/p53 signaling pathway apoptosis, working directly in the lens epithelial cells [44][45][46][47][48].…”