Cell damage (also known as cellular injury) is a variety of stress changes that a cell undergoes due to external as well as internal environmental changes. Among other causes, it can be due to physical, chemical, infectious, biological, nutritional or immunological factors. Cellular damage can be reversible or irreversible. Depending on the degree of damage, the cellular response may be adaptive and, if possible, homeostasis is restored[1]. Cell death occurs when the severity of damage exceeds the cell's ability to self-repair[2]. Cell death depends on both the duration of exposure to the noxious stimulus and the severity of the damage caused[1]. Cell death can occur by necrosis or apoptosis.

Contents

1 Causes

2 Purposes

3 Types of damage

3.1 Reversible damage

3.1.1 Cellular oedema

3.1.2 Changes in fat metabolism

3.2 Irreversible damage

3.2.1 Necrosis

3.2.2 Apoptosis

4 Recovery

4.1 Regeneration

4.2 Replacement

5 Biochemical changes in cellular damage

6 DNA damage and repair

6.1 DNA damage

6.2 Repair of damaged DNA

7 See also

8 Literature used

Causes

Physical agents, such as heat or radiation, can damage a cell by literally boiling or coagulating its contents.

Disruption of nutrient supply, such as lack of oxygen or glucose, or impaired adenosine triphosphate (ATP) production can deprive the cell of essential materials needed for survival[3].

Metabolic: hypoxia and ischaemia

Chemical agents

Microbial agents: viruses and bacteria

Immunological agents: allergies and autoimmune diseases such as Parkinson's disease and Alzheimer's disease .

Genetic factors: such as Down syndrome and sickle cell anaemia [4] .

Targets

The most prominent cell components that are targets of cellular damage are DNA and cell membrane .

DNA damage : In human cells, both normal metabolic activity and environmental factors such as ultraviolet radiation and other radiations can cause DNA damage, resulting in up to one million individual molecular lesions per cell per day[5].

Membrane damage: Damage to the cell membrane disrupts cellular electrolytes, such as calcium, which when continuously increased causes apoptosis.

Mitochondrial damage: can occur due to decreased ATP or changes in mitochondrial permeability.

Ribosome damage: damage to ribosomal and cellular proteins, such as protein misfolding, leading to activation of apoptotic enzymes.

Types of damage

Some cellular damage can be repaired after stress is relieved or when compensatory cellular changes occur. Full function may return to the cells, but in some cases the extent of damage will remain[6].

Reversible damage

Cellular oedema

Cellular oedema (or mast oedema) can occur due to cellular hypoxia that damages the sodium-potassium membrane pump; it is reversible when the cause is removed[7]. Cellular oedema is the first manifestation of almost all forms of cellular damage. When it affects many cells in an organ, it causes some pallor, increased turgor and increased weight of the organ. On microscopic examination, small transparent vacuoles may be seen in the cytoplasm; they represent dilated and detached segments of the endoplasmic reticulum. This type of non-lethal damage is sometimes referred to as hydropic changes or vacuolar degeneration[8]. Hydropic degeneration is a severe form of fat oedema. It occurs in hypokalaemia due to vomiting or diarrhoea.

Ultrastructural changes with reversible cellular damage include:

Blebbing

Blunting

Distortion of microvilli

Weakening of intercellular junctions

Mitochondrial changes

Enlargement of endoplasmic reticulum

Changes in fat metabolism

The damaged cell cannot metabolise fat adequately. Small fat vacuoles accumulate and are dispersed in the cytoplasm. Moderate fatty changes may not affect cell function; however, more severe fatty changes may impair cellular function. In the liver, enlargement of hepatocytes due to fatty changes may compress neighbouring biliary tubules, resulting in cholestasis. Depending on the cause and degree of lipid accumulation, fatty changes are usually reversible. Fatty changes are also known as fatty dystrophy, fatty metamorphosis, or fat steatosis.

Irreversible damage

Necrosis

ange that occurs during cellular injury. This change can occur independently of the provoking agent of cell damage. A decrease in intracellular ATP can have a number of functional and morphological effects during cellular injury. These effects include:

Failure of ATP-dependent pumps ( Na+/K+ pump and Ca2+ pump), resulting in a net influx of Na+ and Ca2+ ions and osmotic swelling.

Cells with depleted ATP stores begin to carry out anaerobic metabolism for energy from glycogen, which is known as ‘glycogenolysis’.

There is a subsequent decrease in the intracellular pH of the cell, which mediates deleterious enzymatic processes.

Early nuclear chromatin adhesion, known as ‘pycnosis’, then occurs and eventually leads to cell death[18].

DNA damage and repair

DNA damage

ase replicates a matrix strand containing a damaged region, it may inaccurately bypass the damage and consequently introduce the wrong base, leading to a mutation. Experimentally, the mutation rate increases significantly in cells defective in DNA mismatch repair [21][22] or homologous recombination repair (HRR)[23].

In both prokaryotes and eukaryotes, DNA genomes are vulnerable to attack by reactive chemicals naturally produced in the intracellular environment and agents from external sources. An important internal source of DNA damage in both prokaryotes and eukaryotes is reactive oxygen species (ROS) formed as by-products of normal aerobic metabolism. For eukaryotes, oxidative reactions are the major source of DNA damage (see DNA damage (natural) and Sedelnikova et al.[24]. ). In humans, about 10,000 oxidative DNA damages occur daily per cell[25]. In rats, which have a higher metabolic rate than humans, there are about 100,000 oxidative DNA damages per cell per day. In aerobically growing bacteria, AFCs appear to be a major source of DNA damage, as indicated by the observation that 89% of spontaneously occurring base-swapping mutations are caused by the introduction of AFC-induced single-stranded damage followed by error-prone replication after this damage. damage[26]. Oxidative DNA damage usually affects only one of the DNA strands at any damaged site, but about 1-2% of damage affects both strands[27]. Double stranded damage includes double strand breaks (DSBs) and interstrand cross-links. For humans, the estimated average average number of endogenous DNA DSBs per cell occurring in each cell generation is about 50[28]. This level of DSB formation probably reflects the natural level of damage caused, in large part, by AFCs produced by active metabolism.

Repair of damaged DNA

Five major pathways are used to repair different types of DNA damage. These five pathways are nucleotide excision repair, base excision repair, mismatch repair, non-homologous end joining and homologous recombination repair (HRR) (see DNA repair ) and source[29]. Only HRR can accurately repair double-stranded lesions such as DSBs. The HRR pathway requires that a second homologous chromosome be available to allow the recovery of information lost by the first chromosome due to double-stranded damage.

DNA damage appears to play a key role in mammalian aging, and an adequate level of DNA repair promotes longevity (see DNA damage aging theory and source). In addition, increased DNA damage and/or reduced DNA repair cause an increased risk of cancer (see Cancer, Carcinogenesis and Neoplasms and source[30]). Furthermore, the ability of HRRs to accurately and efficiently repair double-stranded DNA damage has likely played a key role in the evolution of sexual reproduction (see Evolution of sexual reproduction and source[31]). In modern eukaryotes, HRR during meiosis provides a major advantage in maintaining fertility[31].

[edit | correct code]DNA damage

DNA damage (or RNA damage in the case of some viral genomes) appears to be a fundamental problem for life. As Haynes[19] notes, DNA subunits are not endowed with any particular quantum mechanical stability, and so DNA is vulnerable to all the ‘chemical horrors’ that can befall any such molecule in a warm aqueous environment. These chemical horrors are DNA damages that include various types of DNA base modifications, single- and double-strand breaks, and interstrand crosslinks (see DNA Damage (natural). DNA damage is distinct from mutations, although both are errors in DNA. While DNA damage represents abnormal chemical and structural changes, mutations usually involve the normal four bases in new structures. Mutations can replicate and thus be inherited by DNA replication. In contrast, DNA lesions represent altered structures that cannot themselves be replicated.

Several different repair processes can remove DNA damage (see DNA repair). However, those DNA damages that remain unrepaired can have deleterious effects. DNA damage can block gene replication or transcription. These blockages can lead to cell death. In multicellular organisms, cell death in response to DNA damage can occur through a programmed process, apoptosis[20]. Alternatively, when DNA polymerase replicates a matrix strand containing a damaged region, it may inaccurately bypass the damage and consequently introduce the wrong base, leading to a mutation. Experimentally, the mutation rate increases significantly in cells defective in DNA mismatch repair [21][22] or homologous recombination repair (HRR)[23].

In both prokaryotes and eukaryotes, DNA genomes are vulnerable to attack by reactive chemicals naturally produced in the intracellular environment and agents from external sources. An important internal source of DNA damage in both prokaryotes and eukaryotes is reactive oxygen species (ROS) formed as by-products of normal aerobic metabolism. For eukaryotes, oxidative reactions are the major source of DNA damage (see DNA damage (natural) and Sedelnikova et al.[24]. ). In humans, about 10,000 oxidative DNA damages occur daily per cell[25]. In rats, which have a higher metabolic rate than humans, there are about 100,000 oxidative DNA damages per cell per day. In aerobically growing bacteria, AFCs appear to be a major source of DNA damage, as indicated by the observation that 89% of spontaneously occurring base-swapping mutations are caused by the introduction of AFC-induced single-stranded damage followed by error-prone replication after this damage. damage[26]. Oxidative DNA damage usually affects only one of the DNA strands at any damaged site, but about 1-2% of damage affects both strands[27]. Double stranded damage includes double strand breaks (DSBs) and interstrand cross-links. For humans, the estimated average average number of endogenous DNA DSBs per cell occurring in each cell generation is about 50[28]. This level of DSB formation probably reflects the natural level of damage caused, in large part, by AFCs produced by active metabolism.

[right | right code]Repair of damaged DNA

Five major pathways are used to repair different types of DNA damage. These five pathways are nucleotide excision repair, base excision repair, mismatch repair, non-homologous end joining and homologous recombination repair (HRR) (see DNA repair ) and source[29]. Only HRR can accurately repair double-stranded lesions such as DSBs. The HRR pathway requires that a second homologous chromosome be available to allow the recovery of information lost by the first chromosome due to double-stranded damage.

DNA damage appears to play a key role in mammalian aging, and an adequate level of DNA repair promotes longevity (see DNA damage aging theory and source). In addition, increased DNA damage and/or reduced DNA repair cause an increased risk of cancer (see Cancer, Carcinogenesis and Neoplasms and source[30]). Furthermore, the ability of HRRs to accurately and efficiently repair double-stranded DNA damage has likely played a key role in the evolution of sexual reproduction (see Evolution of sexual reproduction and source[31]). In modern eukaryotes, HRR during meiosis provides a major advantage in maintaining fertility[31].

[edit | right code]See also

Cellular adaptation

[edit | correct code]Literature used

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Hello Naresh,

I'm just checking if you have found the optimal media and stimulation condition to culture b-cells? I'm interested in culturing plasma cells and plasmablasts from primary B-cells obtained from mouse spleen. My goal is to culture these cells and maintain their viability for 1-2 weeks. What type of media and cell activators would you recommend for this?