Double-edged effects of mitochondrial stress on cognitive function / 中国医师杂志

As the populations are aging, concerns about cognitive decline are becoming a common topic in medical consultations. The occurrence of postoperative cognitive change involves many factors such as their own situation and perioperative period. Alzheimer′s disease (AD) is the main concern about postoperative cognitive change. For years it was widely believed that cognitive dysfunction caused by anesthesia, some studies suggest that anesthetics may cause mitochondrial damage, while most studies suggest that mitochondrial dysfunction may affect AD. But it is rarely noticed, that cells can maintain the stability following mitochondrial stress by a series of integrated stress responses (ISR) and alleviate mitochondrial stress in progeny. We reviewed the research progress of mitochondrial stress in AD.

Inhibition of ER Stress by 2-Aminopurine Treatment Modulates Cardiomyopathy in a Murine Chronic Chagas Disease Model

Trypanosoma cruzi infection results in debilitating cardiomyopathy, which is a major cause of mortality and morbidity in the endemic regions of Chagas disease (CD). The pathogenesis of Chagasic cardiomyopathy (CCM) has been intensely studied as a chronic inflammatory disease until recent observations reporting the role of cardio-metabolic dysfunctions. In particular, we demonstrated accumulation of lipid droplets and impaired cardiac lipid metabolism in the hearts of cardiomyopathic mice and patients, and their association with impaired mitochondrial functions and endoplasmic reticulum (ER) stress in CD mice. In the present study, we examined whether treating infected mice with an ER stress inhibitor can modify the pathogenesis of cardiomyopathy during chronic stages of infection. T. cruzi infected mice were treated with an ER stress inhibitor 2-Aminopurine (2AP) during the indeterminate stage and evaluated for cardiac pathophysiology during the subsequent chronic stage. Our study demonstrates that inhibition of ER stress improves cardiac pathology caused by T. cruzi infection by reducing ER stress and downstream signaling of phosphorylated eukaryotic initiation factor (P-elF2α) in the hearts of chronically infected mice. Importantly, cardiac ultrasound imaging showed amelioration of ventricular enlargement, suggesting that inhibition of ER stress may be a valuable strategy to combat the progression of cardiomyopathy in Chagas patients.

Inhibitory effect of coenzyme Q10 on apoptosis of human coronary endothelial cells induced by high glucose and its mechanism / 吉林大学学报(医学版)

Objective: To investigate the inhibitory effect of coenzyme Q10 (Co-QlO) on the apoptosis of human coronary endothelial cells (HCAECs) induced by high glucose, and to elucidate its possible mechanism. Methods: The HCAECs were divided into control group, high glucose group and high glucose combined with 5, 10, and 20 μmol · L-1 Co-QlO treatment groups; the HCAECs in control group were cultured for 24 h using a routine culture method. The cells in high glucose group were treated with 30 mmol · L-1 glucose for 24 h; the cells in high glucose combined with 5, 10, and 20 μmol · L-1 Co-QlO treatment groups were treated with 5, 10, and 20 jumol · L-1 Co-QlO combined with 30 mmol · L-1 glucose for 24 h, respectively. The cell viabilities of HCAECs in various groups were measured by CCK-8 assay. The apoptotic rates of HCAECs in high glucose group and high glucose combined with 10 μmol · L-1 Co-QlO treatment group were detected by Hoechst-PI double staining. The cell mitochondrial membrane potentials of HCAECs in high glucose group and high glucose combined with 10 μmol · L-1 Co-QlO treatment group were determined by Mito-tracker staining. The mitochondrial reative oxygen species (mtROS) levels in the HCAECs in high glucose group and high glucose combined with 10 jumol · L-1 Co-QlO treatment group were measured by MitoSox staining. The protein expression levels of B cell lymphoma/leukemia 2 protein (Bcl-2), Bel-2 assaciated X protein (Bax), Bel-2 assaciated death promoter (Bad) and X-linked inhibitor of apoptosis protein (x-IAP) in the HCAECs in high glucose group and high glucose combined with 10 μmol · L-1 Co-QlO treatment group were detected by Western blotting method. Results: Compared with control group, the cell viability of HCAECs in high glucose group was significantly reduced (P<0. 01); compared with high glucose group, the cell viabilities of HCAECs in high glucose combined with 5, 10, and 20 μmol · L-1 Co-QlO treatment groups were significantly increased (P<0. 05 or P<0. 01), especially in high glucose combined with 10 jumol · L-1 Co-QlO treatment group (P<0. 01). Compared with high glucose group, the apoptotic rate, the mitochondrial membrane potential and the mtROS level of HCAECs in high glucose combined with 10 μmol · L-1 Co-QlO treatment group were significantly decreased (P<0. 01). The Western blotting results showed that compared with high glucose group, the expression levels of Bax and Bad proteins in the HCAECs in high glucose combined with 10 μmol · L-1 Co-QlO treatment group were decreased significantly (P<0. 01), and the expression levels of Bcl-2 and x-IAP proteins were increased significantly (P<0.01). Conclusion: Co-QlO may reduce the apoptosis of HCAECs induced by high glucose through inhibiting the mitochondrial apoptosis-related pathway to ptotect the cells.

Action and mechanism of oxidative stress mediated by TXNIP in diseases / 中国药理学通报

Thioredoxin-interacting protein ( TXNIP) suppresses the antioxidative function of thioredoxin ( Trx ) by combining with thioredoxin ( Trx).Therefore, it promotes the generation and accumulation of reactive oxygen species ( ROS ) , inducing endoplasmic reticulum stress and mitochondrial stress , which leads to cellular inflammation or cellular apoptosis ultimately . TXNIP-mediated oxidative stress plays a crucial role in control-ling the generation and development of some diseases , such as diabetes and its complications ( diabetic nephropathy diabetic retinopathy etc .) , atherosclerosis ischemia/reperfusion injury , cancers ( hepatocellular carcinoma , carcinoma of urinary blad-der, mammary cancer , leukemia ) etc.Here, we try to review the action and mechanism of oxidative stress mediated by TXNIP in the diseases and the progress in research .