The role of sodium hydrosulfide in attenuating the aging process via PI3K/AKT and CaMKKβ/AMPK pathways

Abstract

Age-related dysfunction of the central auditory system, known as central presbycusis, is characterized by defects in speech perception and sound localization. It is important to determine the pathogenesis of central presbycusis in order to explore a feasible and effective intervention method. Recent work has provided fascinating insight into the beneficial function of H2S on oxidative stress and stress-related disease. In this study, we investigated the pathogenesis of central presbycusis and tried to explore the mechanism of H2S action on different aspects of aging by utilizing a mimetic aging rat and senescent cellular model. Our results indicate that NaHS decreased oxidative stress and apoptosis levels in an aging model via CaMKKβ and PI3K/AKT signaling pathways. Moreover, we found that NaHS restored the decreased activity of antioxidants such as GSH, SOD and CAT in the aging model in vivo and in vitro by regulating CaMKKβ and PI3K/AKT. Mitochondria function was preserved by NaHS, as indicated by the following: DNA POLG and OGG-1, the base excision repair enzymes in mitochondrial, were upregulated; OXPHOS activity was downregulated; mitochondrial membrane potential was restored; ATP production was increased; and mtDNA damage, indicated by the common deletion (CD), declined. These effects were also achieved by activating CaMKKβ/AMPK and PI3K/AKT signaling pathways. Lastly, protein homeostasis, indicated by HSP90 alpha, was strengthened by NaHS via CaMKKβ and PI3K/AKT. Our findings demonstrate that the ability to resist oxidative stress and mitochondria function are both decreased as aging developed; however, NaHS, a novel free radical scavenger and mitochondrial protective agent, precludes the process of oxidative damage by activating CaMKKβ and PI3K/AKT. This study might provide a therapeutic target for aging and age-related disease.

Hydrogen sulfide regulates muscle RING finger‐1 protein S‐sulfhydration at Cys44 to prevent cardiac structural damage in diabetic cardiomyopathy

“…Accumulating evidence suggests that production of endogenous H 2 S or the administration of exogenous H 2 S can attenuate myocardial injury after ischaemia or reperfusion and decrease BP and resist oxidative stress (X. Chen et al, 2017;L. Li et al, 2008;D.…”

Exogenous H2S exerts biphasic effects on porcine mammary epithelial cells proliferation through PI3K/Akt‐mTOR signaling pathway

“…As a gaseous signaling molecule, H 2 S exerts its physiological functions through different manners (Nikolic, Li, Liu, & Wang, ), including modifying proteins (Modis et al, ), affecting ion channels (Papapetropoulos et al, ), influencing metabolism (Sun et al, ), and regulating cell signaling such as Nrf 2 pathway (Calvert et al, ), NF‐κB pathway (De Cicco et al, ), PI3 K/Akt pathway (Chen et al, ) and mTOR pathway (Wang et al, ). It has been well documented that the PI3 K/Akt (De Cicco et al, ; Meng, Yuan, et al, ; Meng, Zhang, et al, ) and mTOR (Jiang et al, ; Li et al, ; Pan, Li, Huang, & Zhang, ) signaling pathway are involved in the regulation of the cell proliferation.…”

Exogenous H2S Promoted USP8 Sulfhydration to Regulate Mitophagy in the Hearts of db/db Mice

“…Plasma H2S levels have been reported to decline in an age-dependent manner in human subjects aged 50-80 years, and some studies demonstrated that exogenous H2S contributed to the defense against oxidative damage and mitochondria protection [32]. A recent study reported that exogenous H2S attenuated the aging process via the PI3K/AKT and CaMKKβ/AMPK pathways [33]. In aging cells, damaged mitochondria and proteins accumulate which are toxic to cells and increase ROS production [34].…”