Downregulation of ATP13A2 in midbrain dopaminergic neurons is related to defective autophagy in a mouse model of Parkinson's disease.

Parkinson's disease (PD) is one of the most common diseases of the nervous system characterized by movement disorders arising from loss of midbrain dopaminergic neurons. The relationship between PD and autophagy has received considerable attention. This study aimed to investigate the involvement of the ATP13A2 gene in damage of dopaminergic neurons induced by abnormal autophagy in a MPTP-induced PD mouse model. MPTP was intraperitoneally injected into C57BL mice at 40 mg/kg for 7 days in experimental group. Saline was injected into mice in the control group. After the injection, the mice were tested at different time points for abnormal limb movement by a swimming test. The brain tissue was collected on day 1, 5, and 7 to measure concentration of intracellular calcium. The expression of ATP13A2 was evaluated by real-time PCR. The expression of α-synclein, LC3, LAMP-2, and CaMKK protein was detected by western blot. We found significant motor dysfunction on day 7 in the experimental group, and the expression of α-synclein in the substantia nigra of the midbrain was significantly increased while the expression of ATP13A2 gene was reduced significantly compared with the control group. The concentration of intracellular calcium in the experimental group was significantly higher than in the control group. Autophagy associated proteins LC3-II and LAMP-2 were downregulated and CaMKK protein was upregulated in midbrain tissues of the experimental group compared to control group. In conclusion, our findings suggest that decreased expression of ATP13A2 may lead to defective autophagy and damage to midbrain dopaminergic neurons.

Ghrelin protects small intestinal epithelium against sepsis-induced injury by enhancing the autophagy of intestinal epithelial cells.

BACKGROUND: Ghrelin is a hormone that protects against hypoxic injury of cardiac cells by inducing autophagy, but the role of autophagy in sepsis remains unclear. This study aimed to evaluate whether ghrelin could enhance autophagy in rats with intestinal sepsis. METHODS: The cecal ligation and perforation (CLP) method was used to induce sepsis in Sprague-Dawley rats. The rats were assigned to four groups: normal group, sham-operated group, sepsis group, and Ghrelin-treated group. Sera and small intestinal tissues were collected from all groups. The sepsis was evaluated by histological analysis, and autophagy of small intestinal epithelial cells was assessed by electron microscopy, immunofluorescence, and biochemical methods. RESULTS: The expression of autophagy-associated proteins such as LC3, Atg 7 and Beclin 1 increased by 8h post-CLP and declined to basal levels by 12h post-CLP. The expression of LC3, Atg 7 and Beclin 1 in Ghrelin-treated rats was higher than that in rats with sepsis. Furthermore, compared to rats with sepsis, Ghrelin-treated rats showed significantly reduced intestinal mucosa injury at 20h post-CLP. CONCLUSION: Autophagy is induced in the early stages of sepsis. Ghrelin could enhance the autophagy of intestinal epithelial cells in rats with sepsis and protect the small intestinal epithelium against sepsis-induced injury.

Emodin alleviates lung injury in rats with sepsis.

BACKGROUND: Sepsis has high morbidity and mortality. The aim of this study was to investigate whether emodin, an anthraquinone derived from Chinese herb, exerts protective effects on lung injury in rat model of sepsis. MATERIALS AND METHODS: Forty-eight male Wistar rats were randomly divided into four groups (n = 12): normal group, sham-operated group, cecal ligation and puncture (CLP) model group, and emodin-treated group. Saline or emodin (25 mg/kg) was injected intraperitoneally 0.5 h before CLP. The rats were sacrificed 48 h after CLP. Lung wet-to-dry weight ratio and pathologic changes in the lung were examined, the contents of malondialdehyde and myeloperoxidase in lung tissue were detected, serum tumor necrosis factor alpha and interleukin 6 levels were measured by enzyme-linked immunosorbent assay, and the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) was detected by Western blot analysis. RESULTS: Compared with control group, CLP group exhibited higher wet-to-dry weight ratio and water content in the lung (P < 0.01), but these indexes were reduced and pathologic changes in the lung were relieved in the emodin-treated group. In addition, lung malondialdehyde and myeloperoxidase contents, serum levels of tumor necrosis factor alpha and interleukin 6, and phosphorylation of p38 MAPK increased in the CLP group but decreased in the emodin-treated group (P < 0.05). CONCLUSIONS: Emodin exerts protective effects on lung injury in septic rats, which is related to the inhibition of p38 MAPK pathway and the reduction of oxidative stress and inflammation response during sepsis.

[Significance of erythrocytes phosphatidylserine exposure on occurrence of anemia in sepsis].

OBJECTIVE: To investigate the role of phosphatidylserine (PS) exposure of erythrocytes in the development of anemia in sepsis patients. METHODS: A self-control study was conducted. Thirty sepsis patients admitted to intensive care unit (ICU) were enrolled. Peripheral venous blood was collected on 1 day and 7 days after ICU admission, and hemoglobin (Hb) concentration was examined routinely. A flow-cytometric assay based on Annexin V/ propidium iodide (Annexin V/PI) was used to measure the PS exposure of erythrocytes. The relationship between PS exposure and Hb concentration was analyzed. RESULTS: Hb concentrations in 30 sepsis patients at 7 days after ICU admission were significantly decreased compared with those of patients at 1 day (81.59±3.31 g/L vs. 121.90±3.34 g/L, t=8.570, P=0.000), but the percentage of PS exposure of erythrocytes was significantly higher [(17.19±1.35)% vs. (7.87±0.83)%, t=-6.557, P=0.000]. An inverse correlation was found between percentage of PS-positive RBCs and Hb concentration by Pearson analysis (r=-0.838, P=0.000). CONCLUSIONS: The percentage of PS exposure in erythrocytes is significantly increased in sepsis, and it might contribute to the development of anemia in sepsis patients during hospital stay. The more severe the anemia, the higher the PS in erythrocytes.