Necrosis-Driven Systemic Immune Response Alters SAM Metabolism through the FOXO-GNMT Axis

Obata, Fumiaki; Kuranaga, Erina; Tomioka, Katsura; Ming, Ming; Takeishi, Asuka; Chen, Chun Hong; Soga, Tomoyoshi; Miura, Masayuki

doi:10.1016/j.celrep.2014.03.046

Cited by 75 publications

(107 citation statements)

References 66 publications

Supporting

Mentioning

102

Contrasting

Order By: Relevance

“…In agreement, innate immune responses to tissue damages ( a.k.a . sterile inflammation) were shown to activate FOXO in an invertebrate model (Obata et al., 2014). It is plausible that axonal degeneration due to loss of proteostasis or FOXO function during aging initiates reactive gliosis to prevent further neuronal damage.…”

Section: Discussionmentioning

confidence: 99%

FOXO protects against age‐progressive axonal degeneration

Hwang

Santo

et al. 2017

Aging Cell

View full text Add to dashboard Cite

SummaryNeurodegeneration resulting in cognitive and motor impairment is an inevitable consequence of aging. Little is known about the genetic regulation of this process despite its overriding importance in normal aging. Here, we identify the Forkhead Box O (FOXO) transcription factor 1, 3, and 4 isoforms as a guardian of neuronal integrity by inhibiting age‐progressive axonal degeneration in mammals. FOXO expression progressively increased in aging human and mouse brains. The nervous system‐specific deletion of Foxo transcription factors in mice accelerates aging‐related axonal tract degeneration, which is followed by motor dysfunction. This accelerated neurodegeneration is accompanied by levels of white matter astrogliosis and microgliosis in middle‐aged Foxo knockout mice that are typically only observed in very old wild‐type mice and other aged mammals, including humans. Mechanistically, axonal degeneration in nerve‐specific Foxo knockout mice is associated with elevated mTORC1 activity and accompanying proteotoxic stress due to decreased Sestrin3 expression. Inhibition of mTORC1 by rapamycin treatment mimics FOXO action and prevented axonal degeneration in Foxo knockout mice with accelerated nervous system aging. Defining this central role for FOXO in neuroprotection during mammalian aging offers an invaluable window into the aging process itself.

show abstract

Section: Discussionmentioning

confidence: 99%

FOXO protects against age‐progressive axonal degeneration

Hwang

Santo

et al. 2017

Aging Cell

View full text Add to dashboard Cite

show abstract

“…Several studies have indicated that the wing pouch (WP) region of wing discs might be a suitable model to study regenerative growth (13,24). WP-Gal4 is expressed predominantly in the wing pouch region and haltere discs from the early stage of larvae (21) (Fig. S1E).…”

Section: Resultsmentioning

confidence: 99%

“…Measurement of metabolites was performed using ultra-high-performance liquid chromatography equipped with tandem MS, TQD (UPLC-MS/MS; Waters) based on a previous study (21,36). Immunostaining, fly culture, and other experimental procedures have been performed following protocols.…”

Section: Methodsmentioning

confidence: 99%

“…It is produced by sole SAM synthase (Sams) from the essential amino acid methionine (Met) and ATP, and SAM levels are strongly regulated by Gnmt in Drosophila fat body (21,22). Gnmt consumes excess SAM and produces S-adenosylhomocysteine (SAH), which is further metabolized to homocysteine (Hcy).…”

Section: Significancementioning

confidence: 99%

“…We previously revealed that local necrosis in adult wings resulted in reduced levels of systemic S-adenosylmethionine (SAM) through the up-regulation of glycine N-methyltransferase (gnmt) in the fat body (21). This report is an example of systemic regulation of SAM metabolism in the fat body on epithelial damage.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Tissue nonautonomous effects of fat body methionine metabolism on imaginal disc repair in Drosophila

Kashio

Obata

Zhang

et al. 2016

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

Self Cite

View full text Add to dashboard Cite

Regulatory mechanisms for tissue repair and regeneration within damaged tissue have been extensively studied. However, the systemic regulation of tissue repair remains poorly understood. To elucidate tissue nonautonomous control of repair process, it is essential to induce local damage, independent of genetic manipulations in uninjured parts of the body. Herein, we develop a system in Drosophila for spatiotemporal tissue injury using a temperature-sensitive form of diphtheria toxin A domain driven by the Q system to study factors contributing to imaginal disc repair. Using this technique, we demonstrate that methionine metabolism in the fat body, a counterpart of mammalian liver and adipose tissue, supports the repair processes of wing discs. Local injury to wing discs decreases methionine and S-adenosylmethionine, whereas it increases S-adenosylhomocysteine in the fat body. Fat body-specific genetic manipulation of methionine metabolism results in defective disc repair but does not affect normal wing development. Our data indicate the contribution of tissue interactions to tissue repair in Drosophila, as local damage to wing discs influences fat body metabolism, and proper control of methionine metabolism in the fat body, in turn, affects wing regeneration.

show abstract

The application of metabolomics toward idiopathic pulmonary fibrosis and potential metabolomic value of diverse samples in interstitial lung diseases

Liu

Cheng

Xue

et al. 2023

Precision Medical Sciences

View full text Add to dashboard Cite

Interstitial lung diseases (ILDs), also known as diffuse lung diseases, pose a significant challenge to the respiratory health of individuals worldwide. Among these conditions, idiopathic pulmonary fibrosis (IPF) is one of the most prevalent, contributing substantially to morbidity and mortality. However, IPF is characterized by high heterogeneity, presenting a substantial obstacle to clinical program development and scientific research due to significant variations in disease progression, treatment response, and prognosis. Recent advances in metabolomics have enabled the identification of specific biochemical pathways and disease biomarkers, offering a beacon of hope for patients afflicted with various diseases. Remarkably, metabolomics has made significant strides in ILDs, particularly in IPF. Metabonomics, a branch of life science, provides an in‐depth analysis of metabolic pathways and the specific biological molecular composition of omics, obtained primarily from biological samples such as serum, plasma, pleural effusion, bronchoalveolar lavage fluid, lung surgical biopsy samples, urine, feces, sputum, and cerebrospinal fluid. In this review, we aim to provide a comprehensive overview of the application of metabolomics in ILDs, with a particular focus on IPF. By summarizing the current state of research in this field, we hope to shed light on the latest advances, challenges, and opportunities that metabolomics can provide in managing ILDs.

show abstract

Necrosis-Driven Systemic Immune Response Alters SAM Metabolism through the FOXO-GNMT Axis

Cited by 75 publications

References 66 publications

FOXO protects against age‐progressive axonal degeneration

FOXO protects against age‐progressive axonal degeneration

Tissue nonautonomous effects of fat body methionine metabolism on imaginal disc repair in Drosophila

The application of metabolomics toward idiopathic pulmonary fibrosis and potential metabolomic value of diverse samples in interstitial lung diseases

Contact Info

Product

Resources

About