ArticleThe Journal of experimental medicine2001
Constitutively activated Akt-1 is vital for the survival of human monocyte-differentiated macrophages. Role of Mcl-1, independent of nuclear factor (NF)-kappaB, Bad, or caspase activation.
Article in The Journal of experimental medicine, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
88 citing papers in PubMed, 206 citations in OpenAlex.
- Critical role for antiapoptotic Bcl-xL and Mcl-1 in human macrophage survival and cellular IAP1/2 (cIAP1/2) in resistance to HIV-Vpr-induced apoptosis.The Journal of biological chemistry · 2012Trial
- Review
- Chitinase 3-like protein 1: a diagnostic biomarker for early liver fibrosis in autoimmune liver diseases.Frontiers in immunology · 2025Article
- Delivery of US28 by incoming HCMV particles rapidly attenuates Akt activity to suppress HCMV lytic replication in monocytes.Science signaling · 2024Article
- Redox Regulation of PTEN by Reactive Oxygen Species: Its Role in Physiological Processes.Antioxidants (Basel, Switzerland) · 2024Review
- The PI3K-Akt pathway is a multifaceted regulator of the macrophage response to diverse group BFrontiers in cellular and infection microbiology · 2023Article
- Cubic multi-ions-doped NaBioactive materials · 2022Article
- Akt Plays Differential Roles during the Life Cycles of Acute and Persistent Murine Norovirus Strains in Macrophages.Journal of virology · 2022Article
- Co-culture of pro-inflammatory macrophages and myofibroblasts: Evaluating morphological phenotypes and screening the effects of signaling pathway inhibitors.Physiological reports · 2021Article
- Human Cytomegalovirus Host Interactions: EGFR and Host Cell Signaling Is a Point of Convergence Between Viral Infection and Functional Changes in Infected Cells.Frontiers in microbiology · 2021Review
- BAD inactivation exacerbates rheumatoid arthritis pathology by promoting survival of sublining macrophages.eLife · 2020Article
- Human Cytomegalovirus Glycoprotein-Initiated Signaling Mediates the Aberrant Activation of Akt.Journal of virology · 2020Article
- Human Cytomegalovirus Mediates Unique Monocyte-to-Macrophage Differentiation through the PI3K/SHIP1/Akt Signaling Network.Viruses · 2020Article
- Chitinase 3-like 1 deficiency ameliorates liver fibrosis by promoting hepatic macrophage apoptosis.Hepatology research : the official journal of the Japan Society of Hepatology · 2019Article
- Programmed necrotic cell death of macrophages: Focus on pyroptosis, necroptosis, and parthanatos.Redox biology · 2019Review
- Akt Signaling in Macrophage Polarization, Survival, and Atherosclerosis.International journal of molecular sciences · 2019Review
- Loss of 2 Akt (Protein Kinase B) Isoforms in Hematopoietic Cells Diminished Monocyte and Macrophage Survival and Reduces Atherosclerosis in Ldl Receptor-Null Mice.Arteriosclerosis, thrombosis, and vascular biology · 2019Article
- The phosphatase PPM1A controls monocyte-to-macrophage differentiation.Scientific reports · 2018Article
- Impaired Mitochondrial Microbicidal Responses in Chronic Obstructive Pulmonary Disease Macrophages.American journal of respiratory and critical care medicine · 2017Article
- Association of Increased F4/80Arthritis & rheumatology (Hoboken, N.J.) · 2017Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Recent data from mice deficient for phosphatase and tensin homologue deleted from chromosome 10 or src homology 2 domain-containing 5' inositol phosphatase, phosphatases that negatively regulate the phosphatidylinositol 3-kinase (PI3K) pathway, revealed an increased number of macrophages in these animals, suggesting an essential role for the PI3K pathway for macro-phage survival. Here, we focused on the role of the PI3K-regulated serine/threonine kinase Akt-1 in modulating macrophage survival. Akt-1 was constitutively activated in human macrophages and addition of the PI3K inhibitor, LY294002, suppressed the activation of Akt-1 and induced cell death. Furthermore, suppression of Akt-1 by inhibition of PI3K or a dominant negative (DN) Akt-1 resulted in loss of mitochondrial transmembrane potential, activation of caspases-9 and -3, and DNA fragmentation. The effects of PI3K inhibition were reversed by the ectopic expression of constitutively activated Akt-1 or Bcl-x(L). Inhibition of PI3K/Akt-1 pathway either by LY294002 or DN Akt-1 had no effect on the constitutive or inducible activation of nuclear factor (NF)-kappaB in human macrophages. However, after inhibition of the PI3K/Akt-1 pathway, a marked decrease in the expression of the antiapoptotic molecule Mcl-1, but not other Bcl-2 family members was observed, and Mcl-1 rescued macrophages from LY294002-induced cell death. Further, inhibition of Mcl-1 by antisense oligonucleotides, also resulted in macrophage apoptosis. Thus, our findings demonstrate that the constitutive activation of Akt-1 regulates macrophage survival through Mcl-1, which is independent of caspases, NF-kappaB, or Bad.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.