Related Experiment Video

Updated: May 6, 2026

Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment
04:48

Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment

Published on: January 7, 2015

6.9K

Anthracyclines induce DNA damage response-mediated protection against severe sepsis

Nuno Figueiredo1, Angelo Chora, Helena Raquel

  • 1Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal; Clínica Universitária de Cirurgia I, Centro Hospitalar Lisboa Norte, EPE, 1649-028 Lisboa, Portugal; Gulbenkian Programme for Advanced Medical Education, 2780-156 Oeiras, Portugal; Champalimaud Foundation, 1400-038 Lisboa, Portugal.

Immunity
|November 5, 2013
PubMed

Insights

Low-dose anthracyclines protect against severe sepsis in mice by activating DNA damage response and autophagy in the lungs. This approach offers disease tolerance, independent of pathogen load, highlighting new therapeutic potential.

Area of Science:

  • Immunology
  • Cellular Biology
  • Pharmacology

Background:

  • Severe sepsis is a life-threatening systemic inflammatory condition with high mortality.
  • Current therapeutic options are limited, primarily focusing on organ support.
  • Understanding the underlying mechanisms of sepsis is crucial for developing novel treatments.

Purpose of the Study:

  • To investigate the therapeutic potential of anthracyclines in treating severe sepsis.
  • To elucidate the molecular pathways involved in anthracycline-mediated protection against sepsis.
  • To explore the role of DNA damage response and autophagy in sepsis pathogenesis and treatment.

Main Methods:

  • Utilized a mouse model of severe sepsis.
  • Administered a low-dose regimen of clinically approved anthracyclines.
  • Assessed the impact of anthracyclines on sepsis severity and mortality.
  • Investigated the role of ataxia telangiectasia mutated (Atm) and autophagy-related protein 7 (Atg7) by gene deletion in lung tissue.
  • Evaluated pathogen burden and disease tolerance.

Main Results:

  • Low-dose anthracyclines conferred robust protection against severe sepsis in mice.
  • The protective effect was critically dependent on the activation of DNA damage response and autophagy pathways specifically in the lung.
  • Deletion of Atm or Atg7 in the lung abrogated the protective effects of anthracyclines.
  • Anthracycline treatment conferred disease tolerance, irrespective of pathogen burden.

Conclusions:

  • Clinically approved anthracyclines, at low doses, represent a promising therapeutic strategy for severe sepsis.
  • Activation of DNA damage response and autophagy in the lung is essential for anthracycline-mediated sepsis protection.
  • DNA damage response pathways, including ATM, are key modulators of immune responses and could be targeted for treating inflammatory conditions like sepsis.

More Related Videos

Cell Cycle-specific Measurement of γH2AX and Apoptosis After Genotoxic Stress by Flow Cytometry08:21

Cell Cycle-specific Measurement of γH2AX and Apoptosis After Genotoxic Stress by Flow Cytometry

Published on: September 1, 2019

12.3K
Cecal Ligation Puncture Procedure11:53

Cecal Ligation Puncture Procedure

Published on: May 7, 2011

55.2K

Related Concept Videos

DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
8.5K
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
2.4K
Cellular Injury I: Introduction01:00

Cellular Injury I: Introduction

Cellular injury occurs when a cell cannot maintain homeostasis or adapt to stressors such as hypoxia, toxins, or trauma. Depending on severity and duration, injury may be reversible, allowing recovery, or irreversible, leading to cell death.General Mechanisms of Cell InjuryAlthough causes vary, most cellular injuries arise from a few key mechanisms that disrupt essential functions and often amplify one another. Cell survival depends on the extent and balance of these disturbances.ATP depletion...
95
Hypersensitivity Reactions: Cytolytic Reactions01:01

Hypersensitivity Reactions: Cytolytic Reactions

Type II hypersensitivity involves IgG and IgM antibodies targeting cell surface antigens, leading to cell destruction. This can occur through complement activation, antibody-dependent cell-mediated cytotoxicity (ADCC), or acting as opsonins for phagocytosis. When excessive, these reactions cause significant tissue damage.Drug-induced hemolytic anemia is a common example, where drugs like penicillin or cephalosporins bind to red blood cells, forming drug-protein complexes. These complexes...
221
Acute Inflammation II: Local and Systemic Effects01:25

Acute Inflammation II: Local and Systemic Effects

Acute inflammation produces a coordinated set of local and systemic changes that limit injury, eliminate pathogens, and initiate repair. These responses arise within minutes of infection, trauma, or chemical insult and are driven by vascular alterations and leukocyte-derived mediators. When the stimulus resolves, the reaction typically abates within days.Local EffectsAt the site of injury, arteriolar vasodilation increases blood flow, resulting in redness and warmth. Simultaneously, increased...
84
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.2K