Possible involvement of both endoplasmic reticulum– and mitochondria-dependent pathways in MoMuLV-<i>ts</i>1–induced apoptosis in astrocytes

Liu, Na; Kuang, Xi; Kim, Hun Taek; Stoica, George; Qiang, Wenan; Scofield, Virginia L.; Wong, Patty

doi:10.1080/13550280490448043

Cited by 45 publications

(52 citation statements)

References 52 publications

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“…22,38 Here, we have shown that levels of ER stress markers, GRP78 and cleavage of procaspase-12 were also increased in Atm À/À astrocytes (Figure 3a).…”

Section: Atm-deficient Astrocytes Show Signs Of Oxidative Stress and mentioning

confidence: 88%

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ATM deficiency induces oxidative stress and endoplasmic reticulum stress in astrocytes

Liu

Stoica

Yan

et al. 2005

Laboratory Investigation

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ATM kinase, the product of the ataxia telangiectasia mutated (Atm) gene, is activated by genomic damage. ATM plays a crucial role in cell growth and development. Here we report that primary astrocytes isolated from ATMdeficient mice grow slowly, become senescent, and die in culture. However, before reaching senescence, these primary Atm À/À astrocytes, like Atm À/À lymphocytes, show increased spontaneous DNA synthesis. These astrocytes also show markers of oxidative stress and endoplasmic reticulum (ER) stress, including increased levels of heat shock proteins (HSP70 and GRP78), malondialdehyde adducts, Cu/Zn superoxide dismutase, procaspase 12 cleavage, and redox-sensitive phosphorylation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2). In addition, HSP70 and ERK1/2 phosphorylation are upregulated in the cerebella of ATMdeficient mice. This increase in ERK1/2 phosphorylation is seen primarily in cerebellar astrocytes, or Bergmann glia, near degenerating Purkinje cells. ERK1/2 activation and astrogliosis are also found in other parts of the brain, for example, the cortex. We conclude that ATM deficiency induces intrinsic growth defects, oxidative stress, ER stress, and ERKs activation in astrocytes.

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“…22,38 Here, we have shown that levels of ER stress markers, GRP78 and cleavage of procaspase-12 were also increased in Atm À/À astrocytes (Figure 3a).…”

Section: Atm-deficient Astrocytes Show Signs Of Oxidative Stress and mentioning

confidence: 88%

“…[14][15][16][17] Loss of astrocytic antioxidant support may contribute to neuronal death. [18][19][20][21][22][23] The findings of one study suggest that Atm À/À astrocytes are unable to protect Purkinje cells against oxidative stress. 9 However, it is not clear how Atm À/À astrocytes fail to protect these neurons.…”

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confidence: 99%

ATM deficiency induces oxidative stress and endoplasmic reticulum stress in astrocytes

Liu

Stoica

Yan

et al. 2005

Laboratory Investigation

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“…As pointed out by Adams (2003) in their review, apoptosis can be simultaneously mediated by two or more signal pathways, but their relative importance is different in response to specific stimuli. For instance, many cell types such as astrocytes (Liu et al 2004), mouse embryonic fibroblasts (Masud et al 2007;Sanges and Marigo 2006), Hela cells (Xu et al 2006), and human teratoma cells (Ferreiro et al 2008) undergo apoptosis through both mitochondrial and ER pathway, and there is evidence showing that both death receptor and mitochondrial pathway simultaneously contribute to disc cell apoptosis (Park et al 2005). We thus hypothesize that mitochondria and the ER might also be co-involved in disc cell apoptosis and therefore play a role in IVDD.…”

Section: Introductionmentioning

confidence: 93%

Both endoplasmic reticulum and mitochondria are involved in disc cell apoptosis and intervertebral disc degeneration in rats

Zhao

Zhang

Jiang

et al. 2009

AGE

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Intervertebral disc cell apoptosis occurs through either death receptor or mitochondrial pathway, but whether disc cell apoptosis is also mediated by the endoplasmic reticulum (ER) pathway remains unclear. The objective of this study was to investigate whether ER and mitochondria are co-involved in disc cell apoptosis and intervertebral disc degeneration (IVDD) in rats. Forty-eight rats were used for in vivo experiments. IVDD was characterized by X-ray and histomorphology examination, disc cell apoptosis was detected by TUNEL staining, and the co-involvement of ER and mitochondria in apoptosis was determined by immunohistochemical staining for GRP78, GADD153, caspase-12, and cytochrome C. Additional eight rats were used for annular cell isolation and culture. After sodium nitroprusside treatment, annular cell apoptosis was observed morphologically and quantified by flow cytometry; the expression of biomarkers of ER stress and mitochondrial dysfunction were analyzed by reverse transcriptase PCR (RT-PCR), fluorescence double labeling, and Western blot; and mitochondrial membrane potential was detected by 5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbo cyanine iodide (JC-1) staining. Finally, NS3694 and Z-ATAD-FMK were employed to inhibit the formation of apoptosome complex and the activation of caspase-12, respectively, and apoptotic incidence and caspase-9 activity were assayed. We found that IVDD, induced by unbalanced dynamic and static forces in the rats, was accompanied by increased disc cell apoptosis and enhanced expression of GRP78, GADD153, caspase-12, and cytochrome C. Annular cell apoptosis induced by sodium nitroprusside was confirmed by morphologic observation and flow cytometry. With increased apoptosis, the expression of GRP78, GADD153, and caspase-12 upregulated, mitochondrial membrane potential decreased, and accumulation of cytochrome C in the cytosol manifested. Furthermore, NS3694 and Z-ATAD-FMK dramatically suppress annular cell apoptosis and caspase-9 activity. In conclusion, disc cell apoptosis mediated simultaneously by ER and mitochondria plays a potent role in IVDD.

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“…In the course of virus productive infection, a large amount of viral proteins is synthesized in infected cells, where unfolded or misfolded proteins result in ER stress (23). The accumulation of viral envelope proteins in the ER has been implicated as the trigger of the UPR in several virus infections (6,7,12,52,84). For HBV, there are three envelopment proteins.…”

Section: Discussionmentioning

confidence: 99%

Subversion of Cellular Autophagy Machinery by Hepatitis B Virus for Viral Envelopment

Liu

Wang

et al. 2011

J Virol

239

296

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Autophagy is a conserved eukaryotic mechanism that mediates the removal of long-lived cytoplasmic macromolecules and damaged organelles via a lysosomal degradative pathway. Recently, a multitude of studies have reported that viral infections may have complex interconnections with the autophagic process. The findings reported here demonstrate that hepatitis B virus (HBV) can enhance the autophagic process in hepatoma cells without promoting protein degradation by the lysosome. Mutation analysis showed that HBV small surface protein (SHBs) was required for HBV to induce autophagy. The overexpression of SHBs was sufficient to induce autophagy. Furthermore, SHBs could trigger unfolded protein responses (UPR), and the blockage of UPR signaling pathways abrogated the SHB-induced lipidation of LC3-I. Meanwhile, the role of the autophagosome in HBV replication was examined. The inhibition of autophagosome formation by the autophagy inhibitor 3-methyladenine (3-MA) or small interfering RNA duplexes targeting the genes critical for autophagosome formation (Beclin1 and ATG5 genes) markedly inhibited HBV production, and the induction of autophagy by rapamycin or starvation greatly contributed to HBV production. Furthermore, evidence was provided to suggest that the autophagy machinery was required for HBV envelopment but not for the efficiency of HBV release. Finally, SHBs partially colocalized and interacted with autophagy protein LC3. Taken together, these results suggest that the host's autophagy machinery is activated during HBV infection to enhance HBV replication.Hepatitis B virus (HBV) is a noncytopathic, enveloped DNA virus that belongs to the family Hepadnaviridae (57, 70). It is one of the most successful human pathogens, with an estimated 2 billion people infected worldwide, of whom 400 million have chronic HBV infection (54). Chronic HBV infection is correlated with a strongly increased risk for the development of liver cirrhosis and hepatocellular carcinoma (HCC) (49, 54).Effective preventive vaccines against HBV have been available for nearly three decades; however, their effectiveness in preventing blood-borne transmission from an infected mother to her newborn is about 90% (77), and therapeutic vaccines for the treatment of established hepatitis B infection are not available (65, 67). Currently, two types of antiviral therapies are approved: pegylated alpha interferon and nucleoside/nucleotide analogues (60). However, these antivirals cannot completely eradicate the virus, and their efficacy in preventing liver cirrhosis and HCC is limited (21, 64). Thus, the details of the host-virus relationship during HBV infection urgently need to be further clarified to facilitate the development of efficient therapeutic strategies for the control of HBV infection.Autophagy, an evolutionarily conserved intracellular process, involves the formation of a double membrane structure, called the autophagosome, which engulfs long-lived cytoplasmic macromolecules and damaged organelles and delivers them to lysosomes for degrada...

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Possible involvement of both endoplasmic reticulum– and mitochondria-dependent pathways in MoMuLV-ts1–induced apoptosis in astrocytes

Cited by 45 publications

References 52 publications

ATM deficiency induces oxidative stress and endoplasmic reticulum stress in astrocytes

ATM deficiency induces oxidative stress and endoplasmic reticulum stress in astrocytes

Both endoplasmic reticulum and mitochondria are involved in disc cell apoptosis and intervertebral disc degeneration in rats

Subversion of Cellular Autophagy Machinery by Hepatitis B Virus for Viral Envelopment

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