UVB-induced apoptosis

Last updated

UVB-induced apoptosis is the programmed cell death of cells that become damaged by ultraviolet rays. This is notable in skin cells, to prevent melanoma. Some studies have shown that exercise accelerates this process.

Contents

Description

Apoptosis is a physiological process, that promotes the active suicide of cells, resulting in an advantage, unlike necrosis which occurs from trauma. In the average human adult it is estimated that 50 to 70 billion cells die each day from apoptosis. One of the largest promoters of apoptosis is exposure to ultraviolet (UV) light. While UV light is essential to human life it can also cause harm by inducing cancer, immunosuppression, photoaging, inflammation, and cell death. [1]

Of the various components of sunlight, ultraviolet radiation B (UVB) (290-320 nm) is considered to be the most harmful. This type of radiation acts primarily on the epidermis, and in particular the keratinocytes. Keratinocytes are known to form a barrier to provide a layer of protection within the skin against environmental hazards. Within the epidermis, in addition to the keratinocytes, there are melanocytes (melanin producing cells). These cells produce pigment that provides the keratinocytes with protection against UVB radiation. Once the keratinocytes have been damaged irreparably as a result of UVB radiation, they are marked for destruction by apoptosis to eliminate them as they are potentially mutagenic cells. Failure of the body to remove DNA damaged cells increases the risk of skin cancer. [2]

One consequence of acute UVB exposure is the occurrence of sunburn cells, keratinocytes, within the epidermis. [3] [4] It has been found that when exposed to UVB radiation the DNA in an epidermis cell undergoes fragmentation, which could result in the growth of tumor cells. To prevent this the cell undergoes a morphological change into keratinocytes. These keratinocytes exhibit the capacity to release TNF-α (tumor necrosis factor - alpha) [5] that stop the growth of the tumor by promoting the death of the cell.

If keratinocyte cells have been damaged by UVB radiation, the term "sunburn cell" or "SBC formation" is used. It is thought that when keratinocytes have been damaged by UVB radiation, this triggers a series of processes, caused in part by damage to the DNA. A study indicates that it may be at the mitochondria where the various processes (ligan-dependent receptor activation and cytosolic signaling) pathways are activated by the production of reactive oxygen species (ROS) that may direct the destruction of keratinocytes through apoptosis by activating caspase. As a result of increased exposure to an oxygen-reduced environment, this promotes the development of ROS thereby linking the incidence of ROS with keratinocytes and making these cells more sensitive to UVB radiation. A study by Tobi et al., in 2002 has linked ROS with cytotoxicity, apoptosis, mutations, and carcinogenesis. Mild hypoxia (1-5%) sensitized keratinocytes to UVB-induced apoptosis, while protecting melanocytes from environmental stresses. [ citation needed ]

A study by Mark Schotanus, et al., has demonstrated that in addition to potential damage to keratinocytes and melanocytes, exposure to UVB radiation may also produce a loss of potassium ions, which may then cause the activation of apoptotic pathways in lymphocytes and neuronal cells as opposed to keratinocytes and melanocytes. It has been demonstrated that incubation of lymphocytes and neuronal cells in elevated concentrations of potassium ions provides protection from apoptosis. This phenomenon was demonstrated in tears, which have higher levels of potassium ions, and bathe cells of the eye and therefore provides protection from UVB radiation. Reduction of potassium ions promotes apoptosis and the synthesis of initiator caspase-8 and the effector caspase-3. [6]

A study reported in the International Journal of Molecular Sciences in 2012; 13(3), pages 2560-2675, published February 28, 2012 by Terrerence J. Piva, Catherine M. Davern, Paula M. Hall, Clay M. Winterford and Kay A.O. Ellem, that while caspase may play a role in apoptosis, it is specifically not as a result of caspase-3. It was reported in that study that the process of apoptosis includes: "detachment from the substrate, followed by loss of specialized membrane structures such as microvilli. The cell then undergoes rounding, shrinkage and blabbing before condensation of chromatin is observed in the nucleus. After a period of time the cell fragments into apoptotic bodies, which in vivo are engulfed and degraded by phagocytic cells such as macrophages" [7] Caspase I is involved in the aforementioned cell membrane activity but not caspase-3. [ citation needed ]

UVB-induced apoptosis pathway

The sequence of events that leads to apoptosis is multifaceted and complex. Despite the simple concept of apoptosis, the sequence of events that leads to it and other conditions that attempt to counter act it can be very cumbersome. [8] Since apoptosis is a last resort alternative, it takes the initiation of multiple other genes (ING2, p53, or Ras subfamily) expressed before the cell is finally programmed for death. In addition, genes like Survivin can attempt to suppress apoptosis. [9]

Related Research Articles

<span class="mw-page-title-main">Apoptosis</span> Type of programmed cell death in multicellular organisms

Apoptosis is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation, and mRNA decay. The average adult human loses 50 to 70 billion cells each day due to apoptosis. For the average human child between 8 and 14 years old, each day the approximate loss is 20 to 30 billion cells.

<span class="mw-page-title-main">Ultraviolet</span> Energetic, invisible radiant energy range

Ultraviolet radiation, also known as simply UV, is electromagnetic radiation of wavelengths of 10–400 nanometers, shorter than that of visible light, but longer than X-rays. UV radiation is present in sunlight, and constitutes about 10% of the total electromagnetic radiation output from the Sun. It is also produced by electric arcs, Cherenkov radiation, and specialized lights, such as mercury-vapor lamps, tanning lamps, and black lights.

<span class="mw-page-title-main">Necrosis</span> Unprogrammed cell death caused by external cell injury

Necrosis is a form of cell injury which results in the premature death of cells in living tissue by autolysis. The term "necrosis" came about in the mid-19th century and is commonly attributed to German pathologist Rudolf Virchow, who is often regarded as one of the founders of modern pathology. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated digestion of cell components. In contrast, apoptosis is a naturally occurring programmed and targeted cause of cellular death. While apoptosis often provides beneficial effects to the organism, necrosis is almost always detrimental and can be fatal.

<span class="mw-page-title-main">Melanocyte</span> Melanin-producing cells of the skin

Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer of the skin's epidermis, the middle layer of the eye, the inner ear, vaginal epithelium, meninges, bones, and heart found in many mammals and birds. Melanin is a dark pigment primarily responsible for skin color. Once synthesized, melanin is contained in special organelles called melanosomes which can be transported to nearby keratinocytes to induce pigmentation. Thus darker skin tones have more melanosomes present than lighter skin tones. Functionally, melanin serves as protection against UV radiation. Melanocytes also have a role in the immune system.

<span class="mw-page-title-main">Skin cancer</span> Medical condition involving uncontrolled growth of skin cells

Skin cancers are cancers that arise from the skin. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. It occurs when skin cells grow uncontrollably, forming malignant tumors. The primary cause of skin cancer is prolonged exposure to ultraviolet (UV) radiation from the sun or tanning devices. Skin cancer is the most commonly diagnosed form of cancer in humans. There are three main types of skin cancers: basal-cell skin cancer (BCC), squamous-cell skin cancer (SCC) and melanoma. The first two, along with a number of less common skin cancers, are known as nonmelanoma skin cancer (NMSC). Basal-cell cancer grows slowly and can damage the tissue around it but is unlikely to spread to distant areas or result in death. It often appears as a painless raised area of skin that may be shiny with small blood vessels running over it or may present as a raised area with an ulcer. Squamous-cell skin cancer is more likely to spread. It usually presents as a hard lump with a scaly top but may also form an ulcer. Melanomas are the most aggressive. Signs include a mole that has changed in size, shape, color, has irregular edges, has more than one color, is itchy or bleeds.

<span class="mw-page-title-main">Keratinocyte</span> Primary type of cell found in the epidermis

Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the basal layer of the skin are sometimes referred to as basal keratinocytes. Keratinocytes form a barrier against environmental damage by heat, UV radiation, water loss, pathogenic bacteria, fungi, parasites, and viruses. A number of structural proteins, enzymes, lipids, and antimicrobial peptides contribute to maintain the important barrier function of the skin. Keratinocytes differentiate from epidermal stem cells in the lower part of the epidermis and migrate towards the surface, finally becoming corneocytes and eventually being shed, which happens every 40 to 56 days in humans.

<span class="mw-page-title-main">Epidermis</span> Outermost of the three layers that make up the skin

The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water released from the body into the atmosphere through transepidermal water loss.

<span class="mw-page-title-main">Sun tanning</span> Darkening of skin in response to ultraviolet light

Sun tanning or tanning is the process whereby skin color is darkened or tanned. It is most often a result of exposure to ultraviolet (UV) radiation from sunlight or from artificial sources, such as a tanning lamp found in indoor tanning beds. People who deliberately tan their skin by exposure to the sun engage in a passive recreational activity of sun bathing. Some people use chemical products that can produce a tanning effect without exposure to ultraviolet radiation, known as sunless tanning.

<span class="mw-page-title-main">Reactive oxygen species</span> Highly reactive molecules formed from diatomic oxygen (O₂)

In chemistry and biology, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (O2), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (O2H), superoxide (O2-), hydroxyl radical (OH.), and singlet oxygen. ROS are pervasive because they are readily produced from O2, which is abundant. ROS are important in many ways, both beneficial and otherwise. ROS function as signals, that turn on and off biological functions. They are intermediates in the redox behavior of O2, which is central to fuel cells. ROS are central to the photodegradation of organic pollutants in the atmosphere. Most often however, ROS are discussed in a biological context, ranging from their effects on aging and their role in causing dangerous genetic mutations.

<span class="mw-page-title-main">Karyorrhexis</span> Destructive fragmentation of the nucleus of a dying cell

Karyorrhexis is the destructive fragmentation of the nucleus of a dying cell whereby its chromatin is distributed irregularly throughout the cytoplasm. It is usually preceded by pyknosis and can occur as a result of either programmed cell death (apoptosis), cellular senescence, or necrosis.

<span class="mw-page-title-main">Cell death</span> Biological cell ceasing to carry out its functions

Cell death is the event of a biological cell ceasing to carry out its functions. This may be the result of the natural process of old cells dying and being replaced by new ones, as in programmed cell death, or may result from factors such as diseases, localized injury, or the death of the organism of which the cells are part. Apoptosis or Type I cell-death, and autophagy or Type II cell-death are both forms of programmed cell death, while necrosis is a non-physiological process that occurs as a result of infection or injury.

Cell damage is a variety of changes of stress that a cell suffers due to external as well as internal environmental changes. Amongst other causes, this can be due to physical, chemical, infectious, biological, nutritional or immunological factors. Cell damage can be reversible or irreversible. Depending on the extent of injury, the cellular response may be adaptive and where possible, homeostasis is restored. Cell death occurs when the severity of the injury exceeds the cell's ability to repair itself. Cell death is relative to both the length of exposure to a harmful stimulus and the severity of the damage caused. Cell death may occur by necrosis or apoptosis.

<span class="mw-page-title-main">Caspase 14</span> Enzyme found in humans

Caspase 14 is an enzyme that in humans is encoded by the CASP14 gene. Orthologs of this gene also exist in other mammals, such as sirenians and cetaceans, though they are inactivated in these two clades. Curiously, manatees, which are sirenians, retain some functional CASP14 genes.

<span class="mw-page-title-main">Sunburn</span> Burning of the skin by the suns radiation

Sunburn is a form of radiation burn that affects living tissue, such as skin, that results from an overexposure to ultraviolet (UV) radiation, usually from the Sun. Common symptoms in humans and other animals include red or reddish skin that is hot to the touch or painful, general fatigue, and mild dizziness. Other symptoms include blistering, peeling skin, swelling, itching, and nausea. Excessive UV radiation is the leading cause of (primarily) non-malignant skin tumors, which in extreme cases can be life-threatening. Sunburn is an inflammatory response in the tissue triggered by direct DNA damage by UV radiation. When the cells' DNA is overly damaged by UV radiation, type I cell-death is triggered and the tissue is replaced.

<span class="mw-page-title-main">Photoaging</span> Ultraviolet light-induced biological development over time

Photoaging or photoageing is a term used for the characteristic changes to skin induced by chronic UVA and UVB exposure. Tretinoin is the best studied retinoid in the treatment of photoaging.

Skin sloughing is the process of shedding dead surface cells from the skin. It is most associated with cosmetic skin maintenance via exfoliation, but can also occur biologically or for medical reasons.

Safingol is a lyso-sphingolipid protein kinase inhibitor. It has the molecular formula C18H39NO2 and is a colorless solid. Medicinally, safingol has demonstrated promising anticancer potential as a modulator of multi-drug resistance and as an inducer of necrosis. The administration of safingol alone has not been shown to exert a significant effect on tumor cell growth. However, preclinical and clinical studies have shown that combining safingol with conventional chemotherapy agents such as fenretinide, vinblastine, irinotecan and mitomycin C can dramatically potentiate their antitumor effects. In phase I clinical trials, it was found to be safe to co-administer with cisplatin, but caused reversible dose-dependent hepatotoxicity.

Immunogenic cell death is any type of cell death eliciting an immune response. Both accidental cell death and regulated cell death can result in immune response. Immunogenic cell death contrasts to forms of cell death that do not elicit any response or even mediate immune tolerance.

<span class="mw-page-title-main">TPEN</span> Chemical compound

TPEN (N,N,N′,N′-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine) is an intracellular membrane-permeable ion chelator. TPEN has a high affinity for many transition metals and should not be considered specific or selective for a particular ion. Chelators can be used in chelation therapy to remove toxic metals in the body. TPEN is a chelator that has a high affinity for zinc. For example, one study showed that TPEN is a stronger chelator compared to other chelators like pentetic acid (DTPA) when high levels of zinc are present (15 μM). When low levels of zinc were present however (0, 3, 6, 9 and 12 μM zinc), there was no significant difference. TPEN is a hexadentate ligand which also forms complexes with other soft metal ions such as Cd2+.

<span class="mw-page-title-main">Rhododendrol</span> Chemical compound

Rhododendrol (RD) also called 4-[(3R)-3-hydroxybutyl]phenol (systemic name), is an organic compound with the formula C10H14O2. It is a naturally occurring ingredient present in many plants, such as the Rhododendron. The phenolic compound was first developed in 2010 as a tyrosinase inhibitor for skin-lightening cosmetics. In 2013, after rhododendrol reportedly caused skin depigmentation in consumers using RD-containing skin-brightening cosmetics, the cosmetics were withdrawn from the market. The skin condition, caused by RD, is called RD-induced leukoderma. Rhododendrol exerts melanocyte cytotoxicity via a tyrosinase-dependent mechanism. It has been shown to impair the normal proliferation of melanocytes through reactive oxygen species-dependent activation of GADD45. It is now well established that rhododendrol is a potent tyrosinase inhibitor.

References

  1. ↑ Schwarz, A; Bhardwaj R; Aragane Y; Mahnke K; Riemann H; Metze D; Luger TA; Schwarz T (June 1995). "Ultraviolet-B-Induced Apoptosis of Keratinocytes: Evidence for partial involvement of tumor necrosis factor alpha in the formation of sunburn cells". The Society for Investigative Dermatology. 104 (6): 922–927. doi:10.1111/1523-1747.ep12606202.
  2. ↑ Free Radical Biology and Medicine, Vol 52, Issue 6, 15 March 2012, Pages 1111-1120. Skin mild hypoxia enhances killing of UVB-damaged keratinocytes through relative oxygen species-mediated apoptosis requiring Nova and Bim. Kris Kys, Hannaelore Maes, Graieia Andrei, Rober Snoeck, Maria Garmyn, Partiizia Agostinis
  3. ↑ Danno, K; Horio, T (1987). "Sunburn cell: factors involved in its formation". Photochem Photobiol. 45: 683–690. doi:10.1111/j.1751-1097.1987.tb07401.x.
  4. ↑ Young, AR (1987). "The sunburn cell". Photodermatology. 4: 127–134.
  5. ↑ Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B (1975). "An endotoxin-induced serum factor that causes necrosis of tumors". Proc Natl Acad Sci USA. 72: 3666–3670. doi:10.1073/pnas.72.9.3666. PMC   433057 . PMID   1103152.
  6. ↑ Experimental Eye Research, Vol 93, Issue 5, November 2011, pages 735-740. Stratified Corneal timbal epithelial cells are protected from UVB-induced apoptosis by elevated extracellular potassium ions. Mark Schotanus, Leah R. Koetje, Rachel E. Van Dyken, John L. Ubels
  7. ↑ Methods 2008; 44; pages 205-221, Apoptosis and necrosis, detection, discrimination and phagocytosis, Krysko D.V. Berghe T.V. D. Herde, K., Vandenabeele P.
  8. ↑ Zhang, W; Hanks A; Boucher K; Florell S; Allen S; Alexndar A; Brash D; Grossman D (2005). "UVB-Induced Apoptosis drives clonal expansion during skin tumor development". Carcinogenesis. 26: 249–257. doi:10.1093/carcin/bgh300. PMC   2292404 . PMID   15498793.
  9. ↑ Pedeux, R.; Sengupta S; Shen JC; et al. (2006). "ING2 Regulates the onset of replicative senescence by induction of p300 dependent p53 acetylation". Mol. Cell. Biol. 25: 6639–48. doi:10.1128/MCB.25.15.6639-6648.2005. PMC   1190357 . PMID   16024799.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.