Sirtuin-3 activates the mitochondrial unfolded protein response and reduces cerebral ischemia/reperfusion injury.

Sirtuin-3 (Sirt3) deacetylates several mitochondrial proteins implicated into cerebral ischemia/reperfusion (I/R) injury. The mitochondrial unfolded protein response (UPRmt) favors mitochondrial proteostasis during various stressors. Here, we used Sirt3 transgenic mice and a transient middle cerebral artery occlusion model to evaluate the molecular basis of Sirt3 on the UPRmt during brain post-ischemic dysfunction. The present study illustrated that Sirt3 abundance was suppressed in the brain after brain ischemic abnormalities. Overexpression of Sirt3 in vivo suppressed the infarction size and attenuated neuroinflammation after brain I/R injury. Sirt3 overexpression restored neural viability by reducing mitochondrial ROS synthesis, maintaining the mitochondrial potential and improving mitochondrial adenosine triphosphate synthesis. Sirt3 overexpression protected neuronal mitochondria against brain post-ischemic malfunction via eliciting the UPRmt by the forkhead box O3 (Foxo3)/sphingosine kinase 1 (Sphk1) pathway. Inhibiting either the UPRmt or the Foxo3/Sphk1 pathway relieved the favorable influence of Sirt3 on neural function and mitochondrial behavior. In contrast, Sphk1 overexpression was sufficient to reduce the infarction size, attenuate neuroinflammation, sustain neuronal viability and prevent mitochondrial abnormalities during brain post-ischemia dysfunction. Thus, the UPRmt protects neural viability and mitochondrial homeostasis, and the Sirt3/Foxo3/Sphk1 pathway is a promosing therapeutic candidate for ischemic stroke.

Effects of nitrogen and phosphorus addition on growth and leaf nitrogen metabolism of alfalfa in alkaline soil in Yinchuan Plain of Hetao Basin.

Alkaline soil is widely distributed in China. Its rational utilization is an effective measure to solve land shortage and improve the environment. Alfalfa is characterized by strong salt and alkali tolerance and high yield and protein content. Nitrogen (N) and phosphorus (P) are the main nutrients for plant growth, and N metabolism is one of the primary forms of plant metabolism, which plays a vital role in quality and yield formation. The exploration of the effect of N and P on N metabolism and alfalfa growth will provide a theoretical basis for scientific fertilization for alfalfa in the alkaline soil of the Yinchuan Plain of the Hetao Basin. Therefore, a 2-year experiment of N and P addition was conducted. Six treatments were set up with a randomized block design, including without N (WN), medium N (MN), high N (HN), without P (WP), medium P (MP), and high P (HP). It was found that the MN and MP treatments increased plant height, stem diameter, stem/leaf, dry/fresh, and dry matter of alfalfa. The HN and HP treatments inhibited alfalfa biomass formation. The MN and MP treatments increased key products and enzymes of leaf N metabolism of alfalfa and promoted activities of leaf nitrate reductase (NR), glutamine synthase (GS), glutamate synthase (GOGAT), glutamic-oxalacetic transaminase (GOT), and glutamic-pyruvate transaminase (GPT), and inhibited activities of leaf protease of alfalfa. The MN and MP treatments increased contents of leaf N, P, ammonium nitrogen (NH4 +-N), nitrate nitrogen (NO3 --N), total chlorophyll, and protein and reduced leaf chlorophyll a/b and amino acid, results after HN and HP treatments were opposite. The correlation among leaf P, N, NO3 --N, amino acid, and protein reached significant levels (P < 0.01). It is suggested that MN and MP treatments can improve the yield and quality of alfalfa by increasing key products and enzymes of N metabolism and can be adopted to promote alfalfa production in the alkaline soil of the Yinchuan Plain of the Hetao Basin.