Extent Of Endoplasmic Reticulum Stress Research Articles

Observation of formaldehyde-induced ER stress by an ER-targeting two-photon probe

The presence of formaldehyde (FA) residue in leather during processing impacts the quality of the leather. Additionally, FA penetrates the nervous system through inhalation and skin contact, resulting in neuroinflammation and the build-up of misfolded proteins in the brain. Furthermore, it disrupts the endoplasmic reticulum, leading to abnormal protein aggregation and endoplasmic reticulum stress. As a result, the development of a dependable approach for monitoring endoplasmic reticulum stress caused by FA in scrap leather is crucial. With this research we developed a two-photon fluorescence probe (SKD-1-HCHO) sensitive to FA and targeting the endoplasmic reticulum. The extent of endoplasmic reticulum stress during the neuroinflammation process induced by scrap leather was investigated. According to the experimental results, the probe displayed a rapid Turn-ON response, remarkable specificity, and high sensitivity toward FA in the two-photon mode. Moreover, the probe exhibited an extensive linear range both in vitro and in cells. The induction of neuroinflammation by scrap leather was observed through BV-2 cells and mice. It was found that the formaldehyde content in scrap leather could induce cellular inflammatory responses, leading to initiation of endoplasmic reticulum stress processes. Significantly, while the anti-inflammatory drug NS-398 could not regulate the formaldehyde levels in cells, it could significantly inhibit cellular inflammation and the process of endoplasmic reticulum stress.

PO-302 The Research on the Effects of Resistance Training on the Stress of Skeletal Muscle Endoplasmic Reticulum and Mitochondrial Autophagy in Aging Rats

Objective By establishing a resistance training model, the researchers observed the effects of resistance exercise on the endoplasmic reticulum stress and mitochondrial autophagy-related factors in aging rats and further discussed the physiological mechanism of resistance movement in preventing and delaying senile skeletal muscle decay .
 Methods 20 adult rats and 20 aged rats were randomly divided into two groups. The adult group was divided into the control Group C and the Sports Group E Group, the elderly group were divided into the control group OC Group and the Sports Group OE Group, 10/group. The eight-week tail-loading ladder training method was used to intervene the suitable resistance training for rats in the exercise group. During this period, rats in the control group did not exercise any training activities and ate normally. The relative expression of PINK1, PARKIN, LC3, PERK/EIF2A and Caspase-12 mRNA in gastrocnemius muscle of rats were detected by quantitative PCR after the experiment. The expression of Pink1/parkin protein in gastrocnemius muscle of rats was detected by Western Blot method. High performance liquid chromatography was performed to detect the ATP production of rat gastrocnemius mitochondria, and the obtained data were collected and analyzed.
 Results (1) Compared with group C, the expression of PINK1 protein and parkin protein of gastrocnemius muscle in OC Group decreased significantly (p<0.05). PINK1 protein and Parkin protein in OE Group increased significantly (p<0.01) compared with OC Group.(2) Compared with group C, the expression of Pink1mRNA, PARKIN mRNA and Lc3 mRNA in OC group showed a downward trend (p<0.05), and the expression of Pink1 mRNA, PARKIN mRNA and Lc3 mRNA in Group E showed an ascending trend (p<0.01). Compared with OC , the expression of Pink1 mRNA, PARKIN mRNA and Lc3 mRNA in OE group increased and had significant difference (p<0.01).(3) Compared with group C, the expression levels of perk mRNA, eif2a mRNA and Caspase-12 mRNA in the gastrocnemius of rats in Group E were significantly lower (p<0.01), and the expression of perk mRNA in OC Group had a significant upward trend (p<0.05). Compared with OC Group , the expression levels of perk mRNA, eif2a mRNA and Caspase-12 mRNA in OE group showed significant decrease (p<0.01).(4) There was a small increase in mitochondrial ATP production in Group E rats and Group C, but there was no significant difference. The mitochondrial ATP production in Group C was significantly higher than that in OC Group, and had significant difference (p<0.01). After 8 weeks ' training, the mitochondrial function of the OE group was restored to normal, and the ATP production in the OC group increased significantly, there was significant difference (p<0.05).
 Conclusions The resistance training can improve the function of mitochondria and activate the autophagy, which can improve the abnormality of mitochondria autophagy caused by skeletal muscle decay. Resistance training can reduce the extent of endoplasmic reticulum stress, suggesting that skeletal muscle decay can be slowed down by prolonged exercise.

Mild Endoplasmic Reticulum Stress Protects Against Lipopolysaccharide-Induced Astrocytic Activation and Blood-Brain Barrier Hyperpermeability.

Recent research has revealed that uncontrolled chronic neuroinflammation is closely associated with diverse neurodegenerative diseases, by impairing blood-brain barrier (BBB) function and astrocytic reaction. Endoplasmic reticulum (ER) stress is conventionally linked to the loss of neuronal structure and function and should be widely attenuated. This notion has been questioned by recent experimental studies, which have shown that non-harmful levels of ER stress had numerous beneficial roles against neurodegeneration, including neuroprotection and inhibition of cytokine production. Here, we investigated the mild ER stress-based regulation of LPS-induced inflammatory responses in astrocytes. Primary astrocytes were exposed to tunicamycin (TM), a compound that activates ER stress, with or without the ER-stress inhibitor sodium 4-phenylbutyrate (4-PBA) before LPS treatment. Astrocytic activation, proinflammatory factor production, and the extent of ER stress were assessed. In addition, the effect of mild ER stress on astrocytes and BBB function was determined in vivo. Male Sprague-Dawley rats received intracerebroventricular injections of TM with or without intraperitoneal 4-PBA before LPS administration. The levels of astrocytic activation and BBB permeability were measured after treatment. Our results showed that lower doses of TM resulted in a mild ER-stress response without inducing cytotoxicity and tissue toxicity. Non-toxic ER-stress preconditioning ameliorated LPS-induced overactivation and inflammatory responses in astrocytes. Moreover, pre-exposure to non-lethal doses of TM improved LPS-induced BBB impairment and cognitive ability dysfunction in rats. However, 4-PBA, reversed the protective effect of TM preconditioning in vitro and in vivo. We conclude that mild ER stress (“preconditioning”) can alleviate LPS-induced astrocytic activation and BBB disruption. Our findings provide a better understanding for the regulatory role of ER stress in neuroinflammation and indicate that mild ER stress might have therapeutic value for the treatment of neurodegenerative diseases.

Endoplasmic Reticulum Stress Is a Mechanism of Self-Progression in Congestive Heart Failure

Endoplasmic reticulum stress (ERS) has been reported in hypertrophic and failing hearts (Circ. 110:705, 2004). In turn, a dilated cardiomyopathy (DCM) results from induction of ERS (Mol. Cell. Biol. 24:8007, 2004). Thus, ERS may represent a mechanism for the self-progression of disease in heart failure. The present study sought to document the presence and extent of ERS in failing hearts removed at the time of cardiac transplantation.

Level of Activation of the Unfolded Protein Response Correlates With Paneth Cell Apoptosis in Human Small Intestine Exposed to Ischemia/Reperfusion

In the intestine, Paneth cells participate in the innate immune response. Their highly secretory function makes them susceptible to environmental conditions that cause endoplasmic reticulum (ER) stress. We investigated whether intestinal ischemia/reperfusion (I/R) induces ER stress, thereby activating the unfolded protein response (UPR), and whether excessive UPR activation affects Paneth cells. In addition, we investigated the consequences of Paneth cell compromise during physical barrier damage. Jejunal I/R was studied using a human experimental model (n = 30 patients). Activation of the UPR was assessed using immunofluorescence for binding protein and quantitative polymerase chain reaction analyses for C/EBP homologous protein (CHOP), growth arrest and DNA-damage inducible protein 34 (GADD34), and X-box binding protein 1 (XBP1) splicing. Paneth cell apoptosis was assessed by double staining for lysozyme and M30. Male Sprague-Dawley rats underwent either intestinal I/R to investigate UPR activation and Paneth cell apoptosis, or hemorrhagic shock with or without intraperitoneal administration of dithizone, to study consequences of Paneth cell compromise during physical intestinal damage. In these animals, bacterial translocation and circulating tumor necrosis factor-α and interleukin-6 levels were assessed. In jejunum samples from humans and rats, I/R activated the UPR and resulted in Paneth cell apoptosis. Apoptotic Paneth cells showed signs of ER stress, and Paneth cell apoptosis correlated with the extent of ER stress. Apoptotic Paneth cells were shed into the crypt lumen, significantly lowering their numbers. In rats, Paneth cell compromise increased bacterial translocation and inflammation during physical intestinal damage. ER stress-induced Paneth cell apoptosis contributes to intestinal I/R-induced bacterial translocation and systemic inflammation.