ROS-Dependent Neuroprotective Effects of NaHS in Ischemia Brain Injury Involves the PARP/AIF Pathway

Background and Aims: Parenterally-administered lipid emulsion (LE) is a key cause of enterocyte apoptosis under total parenteral nutrition, yet the pathogenesis has not been fully understood. CUGBP, Elav-like family member 1 (CELF1) has been recently identified as a crucial modulator of apoptosis, and thus this study sought to investigate its role in the LE-induced apoptosis in vitro. Methods: Caco-2 cells were used as an in vitro model. The cells were treated with varying LEs derived from soybean oil, olive oil or fish oil, and changes in the apoptosis and CELF1 expression were assessed. Rescue study was performed using transient knockdown of CELF1 with specific siRNA prior to LE treatment. Regulation of CELF1 by LE treatment was studied using quantitative real-time PCR and Western blotting. Results: All the LEs up-regulated CELF1expression and induced apoptosis, but only olive oil-supplemented lipid emulsion (OOLE)-induced apoptosis was attenuated by depletion of CELF1. Up-regulation of apoptosis-inducing factor (AIF) was involved in OOLE-induced CELF1 dependent apoptosis. The protein expression of CELF1 was up-regulated by OOLE in a dose- and time-dependent manner, but the mRNA expression of CELF1 was unchanged. Analysis by polysomal profiling and nascent protein synthesis revealed that the regulation of CELF1 by OOLE treatment was mediated by directly accelerating its protein translation. Conclusion: OOLE-induces apoptosis in Caco-2 cells partially through up-regulation of CELF1.

Section: Discussionmentioning

confidence: 78%

Olive Oil-Supplemented Lipid Emulsion Induces CELF1 Expression and Promotes Apoptosis in Caco-2 Cells

Yan

Zhu

Gong

et al. 2017

“…H 2 S is produced naturally in mammalian tissues and exhibits various biological and physiological effects [14-17], such as modulated metabolic state [18], mitochondrial function, cellular redox status, and cell apoptosis [19]. …”

Section: Introductionmentioning

confidence: 99%

Exogenous H2S Protects Against Diabetic Cardiomyopathy by Activating Autophagy via the AMPK/mTOR Pathway

Yang

Zhang

Gao

et al. 2017

Background/Aim: Autophagy plays an important role in cellular homeostasis through the disposal and recycling of cellular components. Hydrogen sulphide (H₂S) is the third endogenous gas that has been shown to confer cardiac protective effects. Given the regulation of autophagy in cardioprotection, this study aimed to investigate the protective effects of H₂S via autophagy during high glucose treatment. Methods: This study investigated the content of H₂S in the plasma as well as myocardial, ultrastructural changes in mitochondria and autophagosomes. This study also investigated the apoptotic rate using Hoechst/PI as well as expression of autophagy-associated proteins and mitochondrial apoptotic proteins in H9C2 cells treated with or without GYY4137. Mitochondria of cardiac tissues were isolated and RCR and ADP/O were also detected. AMPK knockdown was performed with siRNA transfection. Results: In a STZ-induced diabetic model, NaHS treatment not only increased the expression of p-AMPK in diabetic group but further activated cell autophagy. Following 48h high glucose, autophagosomes and cell viability were reduced. The present results showed that autophagy could be induced by H₂S, which was verified by autophagic ultrastructural observation and LC3-I/LC3-II conversion. In addition, the mitochondrial membrane potential (MMP) was significantly decreased. The expressions levels of autophagic-related proteins were significantly elevated. Moreover, H₂S activated the AMPK/rapamycin (mTOR) signalling pathway. Conclusions: Our findings demonstrated that H₂S decreases oxidative stress and protects against mitochondria injury, activates autophagy, and eventually leads to cardiac protection via the AMPK/mTOR pathway.

“…Acting as a neuromodulator, H 2 S exerts anti-inflammatory, anti-apoptotic and antioxidant effects on the central nervous system [14-16]. In the central nervous system, cystathionine β-synthase (CBS) is abundantly expressed, which initiates the trans-sulfuration pathway catalysing the amino acid cysteine (Cys) to H 2 S [17].…”

Section: Introductionmentioning

confidence: 99%

Exogenous Hydrogen Sulfide Ameliorates Diabetes-Associated Cognitive Decline by Regulating the Mitochondria-Mediated Apoptotic Pathway and IL-23/IL-17 Expression in db/db Mice

Zhong

et al. 2017

Background: Diabetes-associated cognitive decline (DACD) is one of the complications of diabetes and leads to cognitive impairment and an increased risk of dementia. However, the exact mechanism of DACD has not been fully characterized, and a successful therapy for this issue has not been established. This study aimed to detect the anti-apoptotic and anti-inflammatory effects of hydrogen sulfide (H₂S) on DACD. Methods: We used a behavioural scoring method, Western blot, TUNEL staining and immunofluorescence staining to investigate the expression of the mitochondrial apoptotic pathway and the IL-23/IL-17 axis in db/db mice with or without sodium hydrosulfide (NaHS) administration. Results: NaHS administration mice exhibited reduced time to find the platform and a shorter swimming distance (P<0.05), while the time spent in the target quadrant was increased compared to that of the db/db group (P<0.05). Pro-apoptotic proteins, including cleaved Caspase-3, cleaved Caspase-9, Bax and cytochrome C, were elevated in the db/db group (P<0.01) but were downregulated in the db/db+NaHS group (P<0.05). Exogenous H₂S decreased the numbers of TUNEL-positive cells in the db/db mice (P<0.05). The Western blot analysis showed that the expression levels of IL-23/IL-17 were lower in the NaHS administration group than in the db/db group (P<0.05). Conclusion: We demonstrated that H₂S improved the spatial learning and memory abilities of the db/db mice by modulating the mitochondrial apoptotic pathway and the IL-23/IL-17 axis, which were found to be associated with DACD. H₂S treatment may help prevent the progression of apoptotic hippocampal neurons in db/db mice and inform the development of a new therapeutic target.