ALBERT

Beschreibung: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 141〈/p〉 〈p〉Author(s): Chao Wang, Yuan Yuan, Jie Wu, Yuanlin Zhao, Xing Gao, Yihua Chen, Chao Sun, Liming Xiao, Pengfei Zheng, Peizhen Hu, Zengshan Li, Zhe Wang, Jing Ye, Lijun Zhang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉While cardiac hypertrophy and heart failure are accompanied by significant alterations in energy metabolism, more than 50–70% of energy is obtained from fatty acid β-oxidation (FAO) in adult hearts under physiological conditions. Plin5 is involved in the metabolism of lipid droplets (LDs) and is highly abundant in oxidative tissues including heart, liver and skeletal muscle. Plin5 protects the storage of triglyceride (TG) in LDs by inhibiting lipolysis, thereby suppressing excess FAO and preventing excessive oxidative stress in the heart. In this study, we investigated the roles of Plin5 in cardiac hypertrophy and heart failure in mice treated with transverse aortic constriction (TAC). The results indicated that Plin5 deficiency aggravated myocardial hypertrophy in the TAC-treated mice and exacerbated the TAC-induced heart failure. We also found that Plin5 deficiency reduced the cardiac lipid accumulation and upregulated the levels of PPARα and PGC-1α, which stimulate mitochondrial proliferation. Moreover, Plin5 deficiency aggravated the TAC-induced oxidative stress. We consistently found that Plin5 knockdown disrupted TG storage and elevated FAO and lipolysis in H9C2 rat cardiomyocytes. In addition, Plin5 knockdown also provoked mitochondrial proliferation and lipotoxic injury in H9C2 cells. In conclusion, Plin5 deficiency increases myocardial lipolysis, elevates FAO and oxidative burden, and thereby exacerbates cardiac hypertrophy and heart failure in TAC-treated mice.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S089158491930471X-fx1.jpg" width="336" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Beschreibung: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 141〈/p〉 〈p〉Author(s): Ningning Wang, Yanan Ma, Zhuoqun Liu, Lei Liu, Keming Yang, Yaguang Wei, Yang Liu, Xin Chen, Xiance Sun, Deliang Wen〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Exposure to fine particular matter (≤2.5 μM, PM〈sub〉2.5〈/sub〉) contributes to increased risk of obesity and type 2 diabetes. Hydroxytyrosol (HT), a simple polyphenol found in virgin olive oil, is considered to be beneficial for cardiovascular and metabolic disorders. The current study determined whether HT could improve PM〈sub〉2.5〈/sub〉-induced adiposity and insulin resistance (IR), and explored the underlying mechanisms. Fifteen adult female C57BL/6j mice on a chow diet were randomly divided into three groups receiving (1) sterile PBS, (2) PM〈sub〉2.5〈/sub〉 suspended in sterile PBS (1 mg/mL) and (3) PM〈sub〉2.5〈/sub〉+HT (50 mg/kg/day). PM〈sub〉2.5〈/sub〉/PBS exposure was administered by oropharynx instillation every other day and HT supplementation was achieved by gavage every day. Four-week PM〈sub〉2.5〈/sub〉 exposure did not affect body weight, but significantly increased visceral fat mass. The abdominal adiposity coincided with adipocyte hypertrophy and proliferation in visceral white adipose tissue (WAT), as well as decreased metabolic activity in brown adipose tissue and subcutaneous WAT. PM〈sub〉2.5〈/sub〉 enhanced the oxidative stress by diminishing antioxidant enzyme activities in liver and serum, whereas contents of 4-hydroxynonenal (4-HNE), malondialdehyde (MDA) levels in liver and serum were elevated. These changes were accompanied by macrophage infiltration and activation of NF-κB pathway in the liver. Moreover, PM〈sub〉2.5〈/sub〉 exposure led to glucose intolerance and insulin insensitivity, impaired hepatic glycogenesis, and decreased insulin-stimulated Akt phosphorylation in peripheral tissues. Importantly, HT treatment prevented PM〈sub〉2.5〈/sub〉-induced visceral adipogenesis, oxidative stress, hepatic inflammation and NF-κB activation, systemic and peripheral IR. In vitro, after HepG2 cells were incubated with PM〈sub〉2.5〈/sub〉 (0, 5, 25, 50, 100 and 200 μg/mL), reduced glutathione depletion and 4-HNE, 8-hydroxy-2'-deoxyguanosine, MDA increment in a dose-dependent manner were observed; likewise, insulin-stimulated glucose uptake decreased in a dose-dependent manner. Further, with antioxidant NAC and NF-κB inhibitor PDTC, we confirmed that HT attenuated PM〈sub〉2.5〈/sub〉-induced IR through restraining NF-κB activation evoked by oxidative stress. In addition, HT could expand gut microbiota richness, reduce pathogenic bacteria and accommodate the microbial architecture in PM〈sub〉2.5〈/sub〉-exposed mice, which were correlated with parameters of adiposity, oxidative stress and glycometabolism. HT could effectively correct imbalanced oxidative stress triggered by PM〈sub〉2.5〈/sub〉, in turn ameliorated NF-κB pathway and insulin signaling. Gut microbiota may mediate the actions of HT.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉A schematic illustration of how HT interfered with PM〈sub〉2.5〈/sub〉-induced oxidative stress and metabolic disorders in vivo and in vitro. vWAT, visceral white adipose tissue; scWAT, subcutaneous WAT; BAT, brown adipose tissue; PPARγ, peroxisome proliferator-activated receptor gamma; C/EBPα, CCAAT/enhancer-binding protein alpha; UCP1, uncoupling protein 1; COX2, cyclooxygenase 2; IL-1β, interleukin 1beta; TNFα, tumor necrosis factor alpha; GSK3β, glycogen synthase kinase 3β; GS, glycogen synthase; ↑indicates increase, ↓indicates decrease.〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0891584919301856-fx1.jpg" width="281" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Beschreibung: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 141〈/p〉 〈p〉Author(s): Li-Min Zhang, Dong-Xue Zhang, Lan Fu, Yan Li, Xu-Peng Wang, Man-Man Qi, Chen-Chen Li, Pan-Pan Song, Xiao-Dong Wang, Xiang-Jun Kong〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Objective〈/h6〉 〈p〉Carbon monoxide (CO) releasing molecule (CORM)-3, a water-soluble CORM, has protective effects against inflammatory and ischemia/reperfusion injury. We determined the effect of CORM-3 against neuronal pyroptosis in a model of hemorrhagic shock and resuscitation (HSR) in rats via mitochondrial regulation.〈/p〉 〈/div〉 〈div〉 〈h6〉Methods〈/h6〉 〈p〉Rats were treated with CORM-3 (4 mg/kg) in vitro after HSR. We measured cortical CO content 3–24 h after HSR; assessed neuronal pyroptosis, mitochondrial morphology, ROS production, and mitochondrial membrane potential at 12 h after HSR; and evaluated brain magnetic resonance imaging at 24 h after HSR and learning ability 30 days after HSR. We also measured soluble guanylate-cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signaling pathway activity using a blocker of sGC, NS2028, and 〈sup〉125〈/sup〉I-cGMP assay.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉Among rats that underwent HSR, CORM-3-treated rats had more CO in the cortical tissue than sham- and iCORM-3-treated rats. CORM-3-treated rats had significantly less neuronal pyroptosis in the cortical tissue; higher sGC activity and cGMP content; lower ROS production; better mitochondrial morphology, function, and membrane potential; and enhanced learning/memory ability than HSR-treated rats. However, these neuroprotective effects of CORM-3 were partially inhibited by NS2028.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusion〈/h6〉 〈p〉CORM-3 may alleviate neuronal pyroptosis and improve neurological recovery in HSR through mitochondrial regulation mediated by the sGC–cGMP pathway. Thus, CO administration could be a promising therapeutic strategy for hemorrhagic shock.〈/p〉 〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉A proposed diagram tying together the observations involved in CORM-3-induced neuroprotection against HSR. HSR increased neuronal pyroptosis, which might be associated with up-regulation of ROS. CORM-3 not only significantly reduced these neuronal pyroptosis, but also improved long-term learning ability and T2-weighted MRI, which might be associated with inhibition of mitochondrial dysfunction through regulating activity in sGC-cGMP signal pathway, whereas NS2028, a blocker of sGC, could partially inhibit these neuroprotective effects.〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S089158491930855X-fx1.jpg" width="441" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Beschreibung: 〈p〉Publication date: September 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Free Radical Biology and Medicine, Volume 141〈/p〉 〈p〉Author(s): 〈/p〉