Inhibition of endoplasmic reticulum stress-activated IRE1α-TRAF2-caspase-12 apoptotic pathway is involved in the neuroprotective effects of telmisartan in the rotenone rat model of Parkinson's disease

Tong, Qiang; Wu, Liang; Jiang, Teng; Ou, Zhou; Zhu, Dong‐Ya

doi:10.1016/j.ejphar.2016.02.042

Cited by 69 publications

(43 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Other research groups have reported that candesartan and other potent AT1R blockers successfully attenuated death of dopaminergic neurons induced by the a-synclein. They reported that the blockade of the Ang II/AT1R axis and upregulation of peroxisome proliferator-activated receptor gamma might reduce inflammation by modulating neurotrophic factors (NFs) that activate neuroprotective pathways (Wang et al, 2014;Sathiya et al, 2013;Tong et al, 2016). In addition, telmisartan was found to attenuate lipopolysaccharide induced NO, TNF-a, interleukin 1 beta (IL1-b) as a possible novel neuroprotective mechanism, reinforcing the hypothesis that brain RAS may regulate memory via neuroinflammation (Montgomery et al, 2012, Nakamura andLipton, 2011;Goel et al, 2015).…”

Section: Neuro-inflammationmentioning

confidence: 86%

Role of brain renin angiotensin system in neurodegeneration: An update

Abiodun¹,

Ola²

2020

Saudi Journal of Biological Sciences

105

View full text Add to dashboard Cite

a b s t r a c tRenin angiotensin system (RAS) is an endocrine system widely known for its physiological roles in electrolyte homeostasis, body fluid volume regulation and cardiovascular control in peripheral circulation. However, brain RAS is an independent form of RAS expressed locally in the brain, which is known to be involved in brain functions and disorders. There is strong evidence for a major involvement of excessive brain angiotensin converting enzyme (ACE)/Angiotensin II (Ang II)/Angiotensin type-1 receptor (AT-1R) axis in increased activation of oxidative stress, apoptosis and neuroinflammation causing neurodegeneration in several brain disorders. Numerous studies have demonstrated strong neuroprotective effects by blocking AT1R in these brain disorders. Additionally, the angiotensin converting enzyme 2 (ACE2)/Angiotensin (1-7)/Mas receptor (MASR), is another axis of brain RAS which counteracts the damaging effects of ACE/Ang II/AT1R axis on neurons in the brain. Thus, angiotensin II receptor blockers (ARBs) and activation of ACE2/Angiotensin (1-7)/MASR axis may serve as an exciting and novel method for neuroprotection in several neurodegenerative diseases. Here in this review article, we discuss the expression of RAS in the brain and highlight how altered RAS level may cause neurodegeneration. Understanding the pathophysiology of RAS and their links to neurodegeneration has enormous potential to identify potentially effective pharmacological tools to treat neurodegenerative diseases in the brain.

show abstract

Section: Neuro-inflammationmentioning

confidence: 86%

Role of brain renin angiotensin system in neurodegeneration: An update

Abiodun¹,

Ola²

2020

Saudi Journal of Biological Sciences

105

View full text Add to dashboard Cite

show abstract

“…Jiang et al revealed that ERS upregulates GRP78 protein levels in human pancreatic cancer cells [53]. In mammalian cells, IRE1α mediates ER stress and is both necessary and sufficient for apoptosis [54]. Shimodaira et al demonstrated that CHOP promotes IRE1α and autophagy, especially under ER stress conditions [55].…”

Section: Discussionmentioning

confidence: 99%

Endoplasmic Reticulum Stress Promotes Autophagy and Apoptosis and Reduces Chemotherapy Resistance in Mutant p53 Lung Cancer Cells

Gan

Zhou

Zhong

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Lung cancer (LC) continues to be one of the most prevalent cancers around the world. During this study we aimed to investigate the involvement of endoplasmic reticulum stress (ERS) in autophagy, apoptosis, and chemotherapy resistance of mutant p53 LC cells. Methods: Immunohistochemistry was employed to help determine the p53 mutation status of cancer cells from 92 primary LC patients, who were subsequently assigned to either the mutant p53 (n = 39) or wild-type p53 group (n = 53). Results: Mutant p53 cells exhibited increased expression of the C/EBP homologous protein (CHOP), glucose-regulated protein 78 (GRP78), and inositol-requiring enzyme-1α (IRE1α). The Mutant p53 cells were also found to be sensitive to chemotherapy and displayed decreased expression of PI3K, Akt, and mTOR. The mutant p53 cell lines were treated with tunicamycin to induce ERS and rapamycin in order to inhibit mTOR. Both agents increased the expression of CHOP, GRP78, IRE1α, LC3-II/LC3-I, Atg5, Atg7, caspase-3, caspase-12, cleaved caspase-3, cleaved caspase-12, as well as decreases in cell proliferation as well as the expression levels of PI3K, Akt, and mTOR. Enhanced levels of cell apoptosis and reduced chemotherapy resistance were also detected. Conclusion: The findings of our study suggest that ERS promotes autophagy and apoptosis, while acting to reduce chemotherapy resistance in mutant p53 LC cells by downregulating the PI3K/Akt/mTOR signaling pathway.

show abstract

“…Activated caspase-12 could be blocked by the administration of EMPA, which showed a similar dose-dependent relationship as the expression of CHOP. The activation of TRAF2 is considered to be a biomarker of ERS, which can activate caspase-12 [39]. TRAF2-JNK is another pathway involved in ER-associated apoptosis [40].…”

Section: Discussionmentioning

confidence: 99%

The Sodium-Glucose Co-Transporter 2 Inhibitor, Empagliflozin, Protects against Diabetic Cardiomyopathy by Inhibition of the Endoplasmic Reticulum Stress Pathway

Zhou¹,

Wu²

2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: This study aimed to determine whether or not the sodium-glucose co-transporter 2 inhibitor, empagliflozin (EMPA), can protect against diabetic cardiomyopathy (DCM) and to elucidate the related mechanism. Methods: Rats were divided into the following four groups: a non-diabetic group; diabetic cardiomyopathy rats without EMPA treatment; and diabetic cardiomyopathy rats with EMPA treatment (low- and high-dose EMPA). Hemodynamic measurements were performed to evaluate left ventricular systolic and diastolic function. The histopathology of the heart was examined with hematoxylin-eosin staining. Expression of glucose-regulated protein (GRP)78, enhancer-binding protein homologous protein (CHOP), and caspase-12 was detected by Western blot, and the mRNA levels of XBP1, ATF4, and TRAF2 were analysed by real-time PCR. Results: EMPA significantly decreased the blood glucose level when compared with vehicle. EMPA strongly improved cardiac function based on hemodynamic and histopathologic analyses. Moreover, EMPA can significantly down-regulate the expression of GRP78, CHOP, and caspase-12 (P < 0.01). Additionally, the mRNA levels of XBP1, ATF4, and TRAF2 were markedly decreased by administration of EMPA (P < 0.01). Conclusion: EMPA protects against DCM by inactivating the endoplasmic reticulum stress pathway.

show abstract

Inhibition of endoplasmic reticulum stress-activated IRE1α-TRAF2-caspase-12 apoptotic pathway is involved in the neuroprotective effects of telmisartan in the rotenone rat model of Parkinson's disease

Cited by 69 publications

References 59 publications

Role of brain renin angiotensin system in neurodegeneration: An update

Role of brain renin angiotensin system in neurodegeneration: An update

Endoplasmic Reticulum Stress Promotes Autophagy and Apoptosis and Reduces Chemotherapy Resistance in Mutant p53 Lung Cancer Cells

The Sodium-Glucose Co-Transporter 2 Inhibitor, Empagliflozin, Protects against Diabetic Cardiomyopathy by Inhibition of the Endoplasmic Reticulum Stress Pathway

Contact Info

Product

Resources

About