Role of ER Stress Response in Photodynamic Therapy: ROS Generated in Different Subcellular Compartments Trigger Diverse Cell Death Pathways

Moserová, Irena; Králová, Jarmila

doi:10.1371/journal.pone.0032972

Cited by 86 publications

(73 citation statements)

References 70 publications

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“…ER is an important cell organelle which performs cellular vital functions, mainly including protein synthesis, protein post- translational modification, protein folding, sorting and trafficking [51]. In responses to many stimuli, ER dysfunction would lead to accumulation of misfolded proteins which eventually results in ER stress [52].…”

Section: Discussionmentioning

confidence: 99%

Protein kinase RNA- like endoplasmic reticulum kinase (PERK) signaling pathway plays a major role in reactive oxygen species (ROS)- mediated endoplasmic reticulum stress- induced apoptosis in diabetic cardiomyopathy

Liu

Zhu

Chen

et al. 2013

Cardiovasc Diabetol

187

113

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BackgroundEndoplasmic reticulum (ER) stress is considered one of the mechanisms contributing to reactive oxygen species (ROS)- mediated cell apoptosis. In diabetic cardiomyopathy (DCM), cell apoptosis is generally accepted as the etiological factor and closely related to cardiac ROS generation. ER stress is proposed the link between ROS and cell apoptosis; however, the signaling pathways and their roles in participating ER stress- induced apoptosis in DCM are still unclear.MethodsIn this study, we investigated the signaling transductions in ROS- dependent ER stress- induced cardiomocyte apoptosis in animal model of DCM. Moreover, in order to clarify the roles of IRE1 (inositol - requiring enzyme-1), PERK (protein kinase RNA (PKR)- like ER kinase) and ATF6 (activating transcription factor-6) in conducting apoptotic signal in ROS- dependent ER stress- induced cardiomocyte apoptosis, we further investigated apoptosis in high- glucose incubated cardiomyocytes with IRE1, ATF6 and PERK- knocked down respectively.Resultswe demonstrated that the ER stress sensors, referred as PERK, IRE1 and ATF6, were activated in ROS- mediated ER stress- induced cell apoptosis in rat model of DCM which was characterized by cardiac pump and electrical dysfunctions. The deletion of PERK in myocytes exhibited stronger protective effect against apoptosis induced by high- glucose incubation than deletion of ATF6 or IRE in the same myocytes. By subcellular fractionation, rather than ATF6 and IRE1, in primary cardiomyocytes, PERK was found a component of MAMs (mitochondria-associated endoplasmic reticulum membranes) which was the functional and physical contact site between ER and mitochondria.ConclusionsROS- stimulated activation of PERK signaling pathway takes the major responsibility rather than IRE1 or ATF6 signaling pathways in ROS- medicated ER stress- induced myocyte apoptosis in DCM.

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Section: Discussionmentioning

confidence: 99%

Protein kinase RNA- like endoplasmic reticulum kinase (PERK) signaling pathway plays a major role in reactive oxygen species (ROS)- mediated endoplasmic reticulum stress- induced apoptosis in diabetic cardiomyopathy

Liu

Zhu

Chen

et al. 2013

Cardiovasc Diabetol

187

113

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“…It is well documented that if the UPR-mediated efforts to correct the protein-folding defect fail, apoptosis ensues [28, 30]. Several mechanisms have been proposed by which apoptotic signals are generated following ER stress [31, 32].…”

Section: Discussionmentioning

confidence: 99%

HIV Tat-Mediated Induction of Human Brain Microvascular Endothelial Cell Apoptosis Involves Endoplasmic Reticulum Stress and Mitochondrial Dysfunction

Lü

Niu

et al. 2014

Mol Neurobiol

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Endoplasmic reticulum (ER) stress triggered under hyperglycemic, hypoxic, and oxidative conditions has been implicated in cellular dysfunction through activation of the unfolded protein response (UPR). Recent clinical studies have documented that the release of soluble cellular and host factors following HIV infection in the central nervous system (CNS) results in induction of the ER stress response. Herein, we demonstrate that exposure of human brain microvascular endothelial cells (HBMECs) to HIV transactivator protein Tat101 resulted in early induction of several major ER stress regulators including ER chaperones Bip/GRP78 and ER stress sensors ATF6, p-PERK, and downstream mediators p-eIF2α and ATF4. Upregulation of the ER stress mediators was accompanied by decreased cell viability and increased apoptosis as evidenced by MTT and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays, respectively. Pretreatment of HBMECs with either ER inhibitor or knockdown of the effector C/EBP homologous protein (CHOP) resulted in increased cell viability and abrogation of apoptosis following Tat exposure. Notably, Tat-mediated activation of the UPR response involved reactive oxygen species. Furthermore, treatment of Tat also resulted in mitochondrial dysfunction, evidenced by decrease in Bcl2/Bax ratio, dysfunction of mitochondrial membrane potential, and release of cytochrome c, all of which could be partially reversed by the ER stress inhibitor. The current study demonstrates that exposure of HBMECs to Tat induces multiple stress responses, including ER stress and mitochondrial dysfunction which in turn lead to apoptosis.

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“…Mitochondrial Ca 2+ loading can stimulate mitochondrial metabolism and subsequently increase generation of ROS. The high mitochondrial ROS level initiates a sequence of events in which oxidative stress increases the probability of Ca 2+ release from ER [38]. The very close proximity between ER and mitochondria leads to the accumulation of Ca 2+ in the mitochondria [39].…”

Section: Er Stress and Rosmentioning

confidence: 99%

An Involvement of Oxidative Stress in Endoplasmic Reticulum Stress and Its Associated Diseases

Bhandary

Marahatta

Kim

et al. 2012

IJMS

344

246

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The endoplasmic reticulum (ER) is the major site of calcium storage and protein folding. It has a unique oxidizing-folding environment due to the predominant disulfide bond formation during the process of protein folding. Alterations in the oxidative environment of the ER and also intra-ER Ca2+ cause the production of ER stress-induced reactive oxygen species (ROS). Protein disulfide isomerases, endoplasmic reticulum oxidoreductin-1, reduced glutathione and mitochondrial electron transport chain proteins also play crucial roles in ER stress-induced production of ROS. In this article, we discuss ER stress-associated ROS and related diseases, and the current understanding of the signaling transduction involved in ER stress.

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Role of ER Stress Response in Photodynamic Therapy: ROS Generated in Different Subcellular Compartments Trigger Diverse Cell Death Pathways

Cited by 86 publications

References 70 publications

Protein kinase RNA- like endoplasmic reticulum kinase (PERK) signaling pathway plays a major role in reactive oxygen species (ROS)- mediated endoplasmic reticulum stress- induced apoptosis in diabetic cardiomyopathy

Protein kinase RNA- like endoplasmic reticulum kinase (PERK) signaling pathway plays a major role in reactive oxygen species (ROS)- mediated endoplasmic reticulum stress- induced apoptosis in diabetic cardiomyopathy

HIV Tat-Mediated Induction of Human Brain Microvascular Endothelial Cell Apoptosis Involves Endoplasmic Reticulum Stress and Mitochondrial Dysfunction

An Involvement of Oxidative Stress in Endoplasmic Reticulum Stress and Its Associated Diseases

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