Mammalian 105 kDa heat shock family proteins suppress hydrogen peroxide‐induced apoptosis through a p38 MAPK‐dependent mitochondrial pathway in HeLa cells

Yamagishi, Nobuyuki; Saito, Youhei; Hatayama, Takumi

doi:10.1111/j.1742-4658.2008.06598.x

Cited by 26 publications

(16 citation statements)

References 65 publications

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“…In the case of PC-12 neuronal cells or NIH-3T3 fibroblasts, interference with p38 kinase activation significantly abrogated apoptosis by nerve growth factor deprivation or UV irradiation (49,55,56). Critically, oxidative stress-induced apoptosis in a variety of cellular systems is suggested to involve activation of p38 MAPK (57). As shown, enforced expression of PE_PGRS11 in alveolar epithelial A549 cells imparted resistance to H 2 O 2 -induced oxidative stress (Fig.…”

Section: Pe_pgrs11-induced Resistance To Oxidative Stress Necessitatementioning

confidence: 69%

The Multifunctional PE_PGRS11 Protein from Mycobacterium tuberculosis Plays a Role in Regulating Resistance to Oxidative Stress

Chaturvedi

Bansal

Narayana

et al. 2010

Journal of Biological Chemistry

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Mycobacterium tuberculosis utilizes unique strategies to survive amid the hostile environment of infected host cells. Infection-specific expression of a unique mycobacterial cell surface antigen that could modulate key signaling cascades can act as a key survival strategy in curtailing host effector responses like oxidative stress. We demonstrate here that hypothetical PE_PGRS11 ORF encodes a functional phosphoglycerate mutase. The transcriptional analysis revealed that PE_PGRS11 is a hypoxia-responsive gene, and enforced expression of PE_PGRS11 by recombinant adenovirus or Mycobacterium smegmatis imparted resistance to alveolar epithelial cells against oxidative stress. PE_PGRS11-induced resistance to oxidative stress necessitated the modulation of genetic signatures like induced expression of Bcl2 or COX-2. This modulation of specific antiapoptotic molecular signatures involved recognition of PE_PGRS11 by TLR2 and subsequent activation of the PI3K-ERK1/2-NF-B signaling axis. Furthermore, PE_PGRS11 markedly diminished H 2 O 2 -induced p38 MAPK activation. Interestingly, PE_PGRS11 protein was exposed at the mycobacterial cell surface and was involved in survival of mycobacteria under oxidative stress. Furthermore, PE_PGRS11 displayed differential B cell responses during tuberculosis infection. Taken together, our investigation identified PE_PGRS11 as an in vivo expressed immunodominant antigen that plays a crucial role in modulating cellular life span restrictions imposed during oxidative stress by triggering TLR2-dependent expression of COX-2 and Bcl2. These observations clearly provide a mechanistic basis for the rescue of pathogenic Mycobacterium-infected lung epithelial cells from oxidative stress.

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Section: Pe_pgrs11-induced Resistance To Oxidative Stress Necessitatementioning

confidence: 69%

The Multifunctional PE_PGRS11 Protein from Mycobacterium tuberculosis Plays a Role in Regulating Resistance to Oxidative Stress

Chaturvedi

Bansal

Narayana

et al. 2010

Journal of Biological Chemistry

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“…JNK and p38 MAPKs are known to be related to cell death (6,7). H 2 O 2 has been shown to increase the activity of JNK and p38 in HeLa cells (22,23). Yamagishi et al (23) demonstrated that HeLa cell apoptosis induced by 500 µM H 2 O 2 was suppressed by treatment with p38 inhibitor but not JNK inhibitor, suggesting that apoptosis occurs through a p38 MAPK-dependent signaling pathway.…”

Section: Discussionmentioning

confidence: 97%

The effect of MAPK inhibitors and ROS modulators on cell growth and death of H2O2-treated HeLa cells

Park

2013

Molecular Medicine Reports

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Reactive oxygen species (ROS) influence the signaling of mitogen‑activated protein kinases (MAPKs) involved in cell survival and death. In the present study, the toxicological effect of hydrogen peroxide (H2O2) on HeLa cervical cancer cells was evaluated following treatment with MAPK inhibitors [MAP kinase or ERK kinase (MEK), c‑Jun N‑terminal kinase (JNK) or p38], N‑acetyl cysteine (NAC) and propyl gallate (PG) (well‑known antioxidants), or L‑buthionine sulfoximine [BSO; an inhibitor of glutathione (GSH) synthesis]. Treatment with 100 µM H2O2 inhibited the growth of HeLa cells and induced cell death, which was accompanied by loss of the mitochondrial membrane potential (MMP; ΔΨm). H2O2 did not induce any specific phase arrests of the cell cycle. ROS levels increased, while GSH levels decreased in H2O2‑treated HeLa cells after 1 and 24 h of treatment. The MAPK inhibitors enhanced H2O2‑induced HeLa cell death, while only p38 inhibitor increased ROS levels. Both NAC and PG attenuated H2O2‑induced HeLa cell growth inhibition and death together with the suppression of ROS levels. BSO increased ROS levels in H2O2‑treated HeLa cells without increasing cell death. The levels of MMP (ΔΨm) loss and GSH depletion were not closely associated with the levels of apoptosis in HeLa cells treated with the MAPK inhibitors, NAC, PG or BSO, in the presence of H2O2. In conclusion, H2O2 induced HeLa cell growth inhibition and death. MAPK inhibitors generally enhanced H2O2‑induced HeLa cell death. In particular, p38 inhibitor increased ROS levels in H2O2‑treated HeLa cells, while NAC and PG attenuated H2O2‑induced HeLa cell death by suppressing ROS levels.

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“…Hsph1 (also called Hsp105 or Hsp110 ) may deserve special attention in this context. Hsph1 is a high molecular weight HSP that functions in cellular stress response and apoptosis pathways (Yamagishi et al, 2008). In our study, Hsph1 was down regulated in liver by three longevity mutations ( Pit1 ( dw/dw ), Prop1 ( df/df ), Ghr (-/-)), and in both kidney and heart in the two mutants evaluated ( Pit1 ( dw / dw ) and Ghr (-/-)).…”

Section: Discussionmentioning

confidence: 99%

Endocrine regulation of heat shock protein mRNA levels in long-lived dwarf mice

Swindell

Masternak

Kopchick

et al. 2009

Mechanisms of Ageing and Development

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Heat shock proteins (HSPs) maintain proteostasis and may protect against age-associated pathology caused by protein malfolding. In C. elegans, the lifespan extension and thermotolerance in mutants with impaired insulin/IGF signals depends partly on HSP elevation. Less is known about the role of HSPs in the increased lifespan of mice with defects in GH/IGF-I pathways. We measured HSP mRNAs in liver, kidney, heart, lung, muscle and cerebral cortex from long-lived Pit1(dw/dw) Snell dwarf mice. We found many significant differences in HSP mRNA levels between dwarf and control mice, but these effects were complex and organ-specific. We noted 15 instances where HSP mRNAs were lower in Pit1(dw/dw) liver, kidney, or heart tissues, and 14/15 of these were also seen in Ghr (-/-) mice, which lack GH receptor. In contrast, of 12 examples where HSP mRNAs were higher in Snell liver, kidney, or heart, none were altered in Ghr(-/-) mice. Four liver mRNAs were depressed in both Pit1(dw/dw) and Ghr(-/-) mice, and each of these was elevated by GH injection in Ames (Prop1(df/df)) dwarf mice, consistent with the hypothesis that these declines depended on GH and/ or IGF-I. Contributions of chaperones to longevity in mice may be more complex than those inferred from C. elegans.

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Mammalian 105 kDa heat shock family proteins suppress hydrogen peroxide‐induced apoptosis through a p38 MAPK‐dependent mitochondrial pathway in HeLa cells

Cited by 26 publications

References 65 publications

The Multifunctional PE_PGRS11 Protein from Mycobacterium tuberculosis Plays a Role in Regulating Resistance to Oxidative Stress

The Multifunctional PE_PGRS11 Protein from Mycobacterium tuberculosis Plays a Role in Regulating Resistance to Oxidative Stress

The effect of MAPK inhibitors and ROS modulators on cell growth and death of H2O2-treated HeLa cells

Endocrine regulation of heat shock protein mRNA levels in long-lived dwarf mice

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