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Related Concept Videos

Caspases01:24

Caspases

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Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
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The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

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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...
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The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

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The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

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Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
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Apoptosis01:30

Apoptosis

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Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
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Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

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Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized...
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Evaluation of Caspase Activation to Assess Innate Immune Cell Death
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Revisiting caspases in sepsis.

M Aziz1, A Jacob1, P Wang1

  • 11] Center for Translational Research, The Feinstein Institute for Medical Research, Manhasset, NY, USA [2] Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, NY, USA.

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Sepsis involves immune system dysfunction, leading to inflammation and later immune suppression. Targeting caspases, key regulators of cell death and inflammation, offers new therapeutic strategies for sepsis.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Pathophysiology

Background:

  • Sepsis is a life-threatening condition characterized by immune dysregulation, progressing from inflammation to immunosuppression.
  • Increased apoptosis contributes to immune suppression, anergy, and organ dysfunction in sepsis.
  • Caspases, intracellular proteases, are crucial in apoptosis, inflammation, and sepsis pathogenesis.

Purpose of the Study:

  • To review the multifaceted roles of caspases in apoptosis, pyroptosis, necroptosis, and inflammation within the context of sepsis.
  • To highlight recent findings linking caspase activity to sepsis pathophysiology.
  • To propose novel therapeutic strategies based on a modernized understanding of sepsis.

Main Methods:

  • Review of recent scientific literature on caspases and sepsis.
  • Analysis of experimental animal and human patient data.
  • Synthesis of findings to elucidate caspase involvement in sepsis.

Main Results:

  • Caspases play critical roles in various cell death pathways (apoptosis, pyroptosis, necroptosis) and inflammatory responses relevant to sepsis.
  • Dysregulated caspase activity contributes significantly to the immune suppression observed in later stages of sepsis.
  • Understanding caspase mechanisms provides new insights into sepsis pathophysiology.

Conclusions:

  • Caspase-mediated cell death and inflammation are central to sepsis progression.
  • Targeting caspases presents a promising avenue for developing novel sepsis therapeutics.
  • Further research into caspase pathways can revolutionize sepsis treatment strategies.