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Related Concept Videos

Overview of Cell Death01:30

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Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
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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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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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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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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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Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
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Ceramides and their roles in programmed cell death.

Martina Bago Pilátová1, Zuzana Solárová1, Roman Mezencev2

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Ceramides regulate programmed cell death, impacting diseases like cancer. Dihydroceramides emerge as key players in cancer progression, offering new therapeutic targets for drug resistance and metastasis.

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Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Medicine

Background:

  • Programmed cell death is vital for organismal health, and its disruption is implicated in numerous diseases.
  • Ceramides are critical signaling molecules influencing various cell death pathways.
  • Dysregulated cell death contributes to disease pathogenesis, highlighting the need to understand its regulators.

Purpose of the Study:

  • To provide a comprehensive overview of ceramides' roles in programmed cell death.
  • To explore the functions of dihydroceramides as emerging bioactive sphingolipids.
  • To discuss the implications of ceramides and dihydroceramides in cancer progression and treatment.

Main Methods:

  • Literature review and synthesis of current research on ceramide signaling.
  • Analysis of ceramide involvement in apoptosis, anoikis, macroautophagy, mitophagy, and necroptosis.
  • Examination of dihydroceramide pathways and their targets.

Main Results:

  • Ceramides modulate diverse programmed cell death pathways, including apoptosis, anoikis, macroautophagy, mitophagy, and necroptosis.
  • Dihydroceramides represent a novel class of sphingolipids with significant downstream effects.
  • Ceramide and dihydroceramide signaling impacts cancer cell growth, drug resistance, and metastasis.

Conclusions:

  • Ceramides are central regulators of multiple programmed cell death forms.
  • Dihydroceramides are emerging as critical mediators in cancer biology.
  • Targeting ceramide and dihydroceramide pathways holds potential for cancer therapy.