The mitochondrial-targeted peptide SBT-20 ameliorates inflammation and oxidative stress in chronic renal failure

Abstract

Chronic renal failure (CRF) is the final outcome of the development of chronic kidney disease with different causes. Although CRF is a common clinical disease, its pathogenesis remains to be improved. SBT-20 belongs to a class of cell-permeable peptides that target the inner mitochondrial membrane, reduce reactive oxygen species (ROS), normalize electron transport chain function, and ATP generation. Our experiment was to evaluate whether SBT-20 affected the oxidative stress and inflammatory process of CRF. The levels of ROS production, mitochondrial membrane potential, NF- κB-p65, TNF-α, Drp1, and mfn2 were measured before and after SBT-20 treatment. We observed that SBT-20 treatment inhibited H2O2-induced mitochondrial ROS production. SBT-20 could also restore the mitochondrial membrane potential and reduce the elevated levels of NF-κB-p65 and TNF-α in HK-2 cells. In vivo , the renal function of CRF mice recovered after treating with SBT-20, the levels of necrotic cells and inflammation decreased, and the morphology of mitochondria recovered. The results showed that SBT-20 had a protective effect on CRF by reducing oxidative stress, inflammation progression via down-regulating of NF-κB-p65, TNF-α, and Drp1 and upregulating of Mfn2. These data support SBT-20 could be used as a potential preparation for CRF.

Reactive oxygen species induced by uric acid promote NRK‑52E cell apoptosis through the NEK7‑NLRP3 signaling pathway

“…Subsequently, it was confirmed that the apoptotic events in nrK-52e cells cultivated under high ua levels were dependent on roS generation. inhibition of ROS has been demonstrated as protective in several experimental cell models, such as hypoxia reoxygenation, unilateral ureteral obstruction (UUO), chronic renal failure and diabetic nephropathy (45)(46)(47)(48). The findings of the present study offered an explanation for the renal cell protective effects of ROS scavengers.…”

Structure-activity relationships of mitochondria-targeted tetrapeptide pharmacological compounds

“…Additionally, our test set included two analogs with φ-B-φ-B register, SS-20, and SPN10. With its Phe/Phe aromatic composition, SS-20 does not possess the free radical scavenging properties of SS-31; however, SS-20 is known to target mitochondria ( Liu et al, 2018 ; Alta et al, 2017 ) and has also demonstrated efficacy with many mitochondrial disease models ( Cho et al, 2007 ; Szeto et al, 2015 ; Yang et al, 2009 ; Sun et al, 2020 ). This confirms that scavenging activity is not an essential feature of the MoA of this class of compounds.…”

“…The pharmacological efficacy of these cationic-aromatic peptides requires that they are cell-permeable and that they target mitochondria. Although these features have been extensively demonstrated for SS-31 (B-φ-B-φ) ( Zhao et al, 2003 ; Zhao et al, 2004 ) and SS-20 (φ-B-φ-B) ( Sun et al, 2020 ) it is not clear if tetrapeptides with other side chain compositions would behave similarly. We therefore compared the cell uptake and mitochondrial localization of N-biotinylated SS-31 (bio-SS-31) and N-biotinylated SPN10 (bio-SPN10), in human kidney epithelial cells (HK-2) and retinal pigment epithelial cells (ARPE-19).…”

Exogenous Bioactive Peptides Have a Potential Therapeutic Role in Delaying Aging in Rodent Models

“…SBT-20 can reduce the expression of mitochondrial mitotic protein Drp1 and increase the expression of mitochondrial fusion protein 2 (Mfn2) to maintain the normal structure and function of mitochondria. SBT-20 treatment can decrease the expression of inflammatory cytokines IL-1β, IL-6, NF-κB1, and NF-κB2 in the kidney and alleviate the symptoms of chronic renal failure (CRF) in CRF mice [85]. Compared with endogenous active peptides, SBT-20 also has regulatory effects on inflammation and oxidative stress.…”