Interferon‐γ induces reactive oxygen species and endoplasmic reticulum stress at the hepatic apoptosis

Watanabe, Yoshifumi; Сузукі, Осаму; Haruyama, Takahiro; Akaike, Toshihiro

doi:10.1002/jcb.10501

Cited by 103 publications

(93 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is also known that UPR can activate proapoptotic gene expression (such as that of GADD153), which in turn can induce infected cells to undergo apoptosis (23,33,61). Expression levels of GADD153 were increased only in rSV5V⌬C-infected cells (consistent with the induction of apoptosis seen in rSV5V⌬C-infected cells).…”

Section: Discussionmentioning

confidence: 57%

Conserved Cysteine-Rich Domain of Paramyxovirus Simian Virus 5 V Protein Plays an Important Role in Blocking Apoptosis

Sun¹,

Rothermel²,

Shuman³

et al. 2004

J Virol

View full text Add to dashboard Cite

The paramyxovirus family includes many well-known human and animal pathogens as well as emerging viruses such as Hendra virus and Nipah virus. The V protein of simian virus 5 (SV5), a prototype of the paramyxoviruses, contains a cysteine-rich C-terminal domain which is conserved among all paramyxovirus V proteins. The V protein can block both interferon (IFN) signaling by causing degradation of STAT1 and IFN production by blocking IRF-3 nuclear import. Previously, it was reported that recombinant SV5 lacking the C terminus of the V protein (rSV5V⌬C) induces a severe cytopathic effect (CPE) in tissue culture whereas wild-type (wt) SV5 infection does not induce CPE. In this study, the nature of the CPE and the mechanism of the induction of CPE were investigated. Through the use of DNA fragmentation, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling, and propidium iodide staining assays, it was shown that rSV5V⌬C induced apoptosis. Expression of wt V protein prevented apoptosis induced by rSV5V⌬C, suggesting that the V protein has an antiapoptotic function. Interestingly, rSV5V⌬C induced apoptosis in U3A cells (a STAT1-deficient cell line) and in the presence of neutralizing antibody against IFN, suggesting that the induction of apoptosis by rSV5V⌬C was independent of IFN and IFN-signaling pathways. Apoptosis induced by rSV5V⌬C was blocked by a general caspase inhibitor, Z-VAD-FMK, but not by specific inhibitors against caspases 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 13, suggesting that rSV5V⌬C-induced apoptosis can occur in a caspase 12-dependent manner. Endoplasmic reticulum stress can lead to activation of caspase 12; compared to the results seen with mock and wt SV5 infection, rSV5V⌬C infection induced ER stress, as demonstrated by increased expression levels of known ER stress indicators GRP 78, GRP 94, and GADD153. These data suggest that rSV5V⌬C can trigger cell death by inducing ER stress.

show abstract

Section: Discussionmentioning

confidence: 57%

Conserved Cysteine-Rich Domain of Paramyxovirus Simian Virus 5 V Protein Plays an Important Role in Blocking Apoptosis

Sun¹,

Rothermel²,

Shuman³

et al. 2004

J Virol

View full text Add to dashboard Cite

show abstract

“…This induction may be due to expression of interferon-g induced during ts1 infection, as demonstrated by recent publications that either interferon-g alone or in concert with TNF-a, is capable of activating the transcription of caspase-12 gene as well as the processing of caspase-12. 49,50 Previous studies have shown that the ER Ca 2 þ ATPase inhibitor Thapsigarin, or Ca 2 þ ionopores induce transcriptional activation of GADD153/ CHOP by elevating intracellular Ca 2 þ . 35,51 We therefore attempted to dissect the mechanism of induction of ER stress signaling pathway in ts1-infected brainstems by investigating Ca 2 þ signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Activation of endoplasmic reticulum stress signaling pathway is associated with neuronal degeneration in MoMuLV-ts1-induced spongiform encephalomyelopathy

Kim

Waters

Stoica

et al. 2004

Laboratory Investigation

View full text Add to dashboard Cite

Temperature-sensitive mutant of Moloney murine leukemia virus-TB (MoMuLV-ts1)-mediated neuronal death in mice is likely due to both loss of glial support and release of cytokines and neurotoxins from ts1-infected glial cells. Cytotoxic mediators present in ts1-induced spongiform lesions may generate endoplasmic reticulum (ER) stress, which has been implicated in the pathogenesis of a variety of neurodegenerative diseases. We investigated whether ER stress signaling is involved in ts1-mediated neuronal loss in the brain of infected mice. ts1-infected brainstems were found to show significant increases in phosphorylation of the double-stranded RNA-dependent protein kinase-like ER kinase and eukaryotic initiation factor 2-a. In addition, increased expression of growth arrest DNA damage 153 (GADD153), glucose-regulated protein 78, and caspase-12 were accompanied by increases in processing of caspase-12 and its downstream target, caspase-3. All of these events are markers of ER stress. We observed that GADD153 and cleaved caspase-3 were present in degenerative neurons in the lesions of infected mice, but not in uninfected controls. Phosphorylated calmodulin-dependent protein kinase II-a was significantly increased, and was coexpressed with GADD153 in a large proportion of neurons undergoing early and advanced degenerative changes. Finally, neuronal degeneration in spongiform lesions was associated with increase in calcium (Ca 2 þ ) accumulation in mitochondria. Together, these results suggest that ts1 infection-mediated neuronal degeneration in mice may result from activation of ER stress signaling pathways, presumably initiated by perturbation of Ca 2 þ homeostasis. Our findings highlight the importance of the ER stress signaling pathway in ts1 infection-induced neuronal degeneration and death.

show abstract

“…Endoplasmic reticulum stress and heart failure Various stimuli, such as hypoxia [132,133] , Ang II stimulation [134] , oxidative stress [135] and inflammatory factors [136] , have been proposed to trigger ERS during heart failure (HF). However, the role of ERS in heart failure is still in dispute.…”

Section: Endoplasmic Reticulum Stress Is Involved In the Development mentioning

confidence: 99%

Endoplasmic reticulum stress: a novel mechanism and therapeutic target for cardiovascular diseases

2016

View full text Add to dashboard Cite

Endoplasmic reticulum is a principal organelle responsible for folding, post-translational modifications and transport of secretory, luminal and membrane proteins, thus palys an important rale in maintaining cellular homeostasis. Endoplasmic reticulum stress (ERS) is a condition that is accelerated by accumulation of unfolded/misfolded proteins after endoplasmic reticulum environment disturbance, triggered by a variety of physiological and pathological factors, such as nutrient deprivation, altered glycosylation, calcium depletion, oxidative stress, DNA damage and energy disturbance, etc. ERS may initiate the unfolded protein response (UPR) to restore cellular homeostasis or lead to apoptosis. Numerous studies have clarified the link between ERS and cardiovascular diseases. This review focuses on ERS-associated molecular mechanisms that participate in physiological and pathophysiological processes of heart and blood vessels. In addition, a number of drugs that regulate ERS was introduced, which may be used to treat cardiovascular diseases. This review may open new avenues for studying the pathogenesis of cardiovascular diseases and discovering novel drugs targeting ERS.

show abstract

Interferon‐γ induces reactive oxygen species and endoplasmic reticulum stress at the hepatic apoptosis

Cited by 103 publications

References 47 publications

Conserved Cysteine-Rich Domain of Paramyxovirus Simian Virus 5 V Protein Plays an Important Role in Blocking Apoptosis

Conserved Cysteine-Rich Domain of Paramyxovirus Simian Virus 5 V Protein Plays an Important Role in Blocking Apoptosis

Activation of endoplasmic reticulum stress signaling pathway is associated with neuronal degeneration in MoMuLV-ts1-induced spongiform encephalomyelopathy

Endoplasmic reticulum stress: a novel mechanism and therapeutic target for cardiovascular diseases

Contact Info

Product

Resources

About