Induced Inhibition of Ischemic/Hypoxic Injury by APIP, a Novel Apaf-1-interacting Protein

Cho, Dong‐Hyung; Hong, Yeon-Mi; Lee, Ho‐June; Woo, Ha-Na; Pyo, Jong-Ok; Mak, Tak W.; Jung, Yong‐Keun

doi:10.1074/jbc.m405747200

Cited by 63 publications

(63 citation statements)

References 39 publications

(26 reference statements)

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“…These distinct activities seem to be assigned to different domains of APIP. As shown in the previous report (Cho et al, 2004), core domain of APIP spanning the common region of APIP and APIP2 was sufficient to suppress etoposide-induced cell death. However, the C-terminal region of APIP rather than core domain is required for the activation of ERK1/2 during hypoxia (Figure 1e).…”

supporting

confidence: 68%

“…Our previous work showed that APIP binds to Apaf-1 and inhibits the intrinsic cell death, postulating that the antiapoptotic activity of APIP lies in its binding ability to Apaf-1 (Cho et al, 2004). From subsequent analyses, however, we observed that the overexpression of APIP further suppressed hypoxia-induced death of Apaf-1(À/ À) mouse embryonic fibroblasts (MEF) cells (Supplementary data Figure 3).…”

mentioning

confidence: 84%

“…The increased expression of APIP in mouse muscle during ischemia/hypoxia is believed to be a necessary step protecting cells from damages (Cho et al, 2004). APIP mRNA was also induced in HepG2 cells, but not in HeLa, NIH3T3 and HEK293T cells (data not shown).…”

mentioning

confidence: 87%

“…APIP functions to inhibit the intrinsic mitochondrial apoptosis pathway including etoposide, staurosporine and hypoxia-induced cell death (Cho et al, 2004). APIP is also highly expressed in muscle and heart and accumulated in mouse muscle during ischemia.…”

mentioning

confidence: 99%

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Suppression of hypoxic cell death by APIP-induced sustained activation of AKT and ERK1/2

Kim

et al. 2006

Oncogene

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Apaf-1-interacting protein (APIP) was previously isolated as an inhibitor of mitochondrial cell death interacting with Apaf-1. Here, we report a hypoxia-selective antiapoptotic activity of APIP that induces the activation of AKT and extracellular signal-regulated kinase (ERK)1/2. Stable expression of APIP in C2C12 (C2C12/APIP) cells suppressed cell death induced by hypoxia and etoposide. Unlike etoposide, however, APIP induces the sustained activation of AKT and ERK1/2 and the phosphorylation of caspase-9 during hypoxia. Inhibition of AKT and ERK1/2 activation by the treatments with phosphatidylinositol 3 0 -kinase and mitogen-activated protein kinase kinase (MEK)1/2 inhibitors sensitized C2C12/APIP cells to hypoxic cell death and abolished the hypoxia-induced phosphorylation of caspase-9. Further, overexpression of phosphorylation-mimic caspase-9 mutants (caspase-9-T125E and caspase-9-S196D), but not phosphorylation-defective caspase-9 mutants (caspase-9-T125A and caspase-9-S196A), effectively suppressed hypoxia-induced death of C2C12 cells. These results elucidate a novel Apaf-1-independent antiapoptotic activity of APIP during hypoxic cell death, inducing the sustained activation of AKT and ERK1/2 and leading to caspase-9 phosphorylation.

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supporting

confidence: 68%

mentioning

confidence: 84%

mentioning

confidence: 87%

mentioning

confidence: 99%

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Suppression of hypoxic cell death by APIP-induced sustained activation of AKT and ERK1/2

Kim

et al. 2006

Oncogene

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“…The association of rs514182 with pyroptosis was surprising, because APIP was previously identified as an inhibitor of a different cell death pathway, the intrinsic (caspase-9-dependent) apoptotic pathway (31). Apoptosis can be induced in LCLs by pharmacologic agents, such as the chemotherapeutic drug carboplatin (20,32).…”

Section: Resultsmentioning

confidence: 99%

Functional genetic screen of human diversity reveals that a methionine salvage enzyme regulates inflammatory cell death

Ko¹,

Gamazon

Shukla³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Genome-wide association studies can identify common differences that contribute to human phenotypic diversity and disease. When genome-wide association studies are combined with approaches that test how variants alter physiology, biological insights can emerge. Here, we used such an approach to reveal regulation of cell death by the methionine salvage pathway. A common SNP associated with reduced expression of a putative methionine salvage pathway dehydratase, apoptotic protease activating factor 1 (APAF1)-interacting protein (APIP), was associated with increased caspase-1-mediated cell death in response to Salmonella. The role of APIP in methionine salvage was confirmed by growth assays with methionine-deficient media and quantitation of the methionine salvage substrate, 5′-methylthioadenosine. Reducing expression of APIP or exogenous addition of 5′-methylthioadenosine increased Salmonellae-induced cell death. Consistent with APIP originally being identified as an inhibitor of caspase-9-dependent apoptosis, the same allele was also associated with increased sensitivity to the chemotherapeutic agent carboplatin. Our results show that common human variation affecting expression of a single gene can alter susceptibility to two distinct cell death programs. Furthermore, the same allele that promotes cell death is associated with improved survival of individuals with systemic inflammatory response syndrome, suggesting a possible evolutionary pressure that may explain the geographic pattern observed for the frequency of this SNP. Our study shows that in vitro association screens of disease-related traits can not only reveal human genetic differences that contribute to disease but also provide unexpected insights into cell biology.HapMap | lymphoblastoid | pyroptosis | quantitative trait | polygenic adaptation

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Apoptosis

Al‐Rubeai

Khoo

Singh

2009

Encyclopedia of Industrial Biotechnology

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Apoptosis is now acknowledged as a fundamentally important process that plays an essential role in embryogenesis and in the maintenance and functionality of the highly ordered cell populations that constitute higher organisms. In this article, we describe the biochemical basis of apoptosis, the morphological changes that accompany it, and some of the techniques that have been used to identify apoptotic cells. This is followed by a general discussion of the regulation and induction of apoptosis. We then describe studies that have investigated this phenomenon from a biotechnological perspective. Particular reference is made to the conditions that elicit an apoptotic response, the cell lines that are susceptible, and the cellular engineering approaches to enhance cell survival and productivity in the bioreactor environment.

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Induced Inhibition of Ischemic/Hypoxic Injury by APIP, a Novel Apaf-1-interacting Protein

Cited by 63 publications

References 39 publications

Suppression of hypoxic cell death by APIP-induced sustained activation of AKT and ERK1/2

Suppression of hypoxic cell death by APIP-induced sustained activation of AKT and ERK1/2

Functional genetic screen of human diversity reveals that a methionine salvage enzyme regulates inflammatory cell death

Apoptosis

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