UVB-induced apoptosis

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UV-induced apoptosis UV-induced apoptosis is an adequate (physiological) reaction of a cell damaged by UV radiation (UVR) in a sufficiently large (lethal) dose and it prevents the disordered destruction of UV damaged cells by help necrosis. Cell elimination by apoptosis occurs when UV-induced cell damage which cannot be repaired by the intracellular repair system exceeds at it certain limit (lethal damage). Through apoptosis, the cells are self-disassembled into compartments with their subsequent utilization (mainly by neighboring cells). The first time sign of the beginning of the apoptosis system is working in a UV damaged cell is the activation of restriction enzymes, which divide cell DNA into fragments convenient for utilization. But too large a dose of UVR can lead to breakdown (inactivation) of the energy-dependent mechanism of apoptosis (super lethal damage). In this case, cell destruction occurs randomly, not orderly, and during a significantly longer (compared with apoptosis) time interval. UV-irradiated cells do not change their appearance for a long time [1, 6], as a result of which the researchers may make the erroneous conclusion that “revealed an unexpected response to a dose at which a higher dose of UV increased the viability of keratinocytes” [2]. The fact that UV-induced apoptosis at high doses of UVR begins to be replaced by necrosis was established in 2000 [3]. For keratinocytes, the proportion of cells that have elimination by help apoptosis, with an increase in UVR dose can reach to achieve 45%, but with a further increase in the dose of UVR (due to the shutdown of the mechanism of apoptosis), destruction of damaged cells by help necrosis and the part of cells that eliminated by apoptosis begins to decrease (non-monotonous dose dependence of UV-induced apoptosis) [4, 11]. In the dose range of UVR from “lethal” to “super-lethal”, “pro-inflammatory” apoptosis can be manifested, which was experimentally discovered in 2003 [5]. This may be the result of partial damage to the apoptosis mechanism by UV radiation [1]. If at moderate doses “pure” apoptosis does not cause an inflammatory reaction, then at sufficiently large (but lower than superlethal) doses, an inflammatory reaction arises due to pro-inflammatory apoptosis, which leads to the appearance of “fast” erythema for UV irradiated skin keratinocytes. Kinetic of “fast” erythema is much faster by the time of development of UV erythema caused by necrosis of UV damaged keratinocytes [6]. The most erythemogenic is UVB (UVB, 280 - 320 nanometers) the spectral range of UVR, since radiation in this range is less absorbed by the outer layers of the skin, which allows UVB radiation, in contrast to UVC (UVC, 200 - 280 nm), to reach more deep layers skin and act on keratinocytes of the deep-lying basal layer of the epidermis of the skin. The ability to induce apoptosis for UVB and UVC radiation is due to the fact that the DNA of the nucleus [7] and / or mitochondria [8] of the cell absorbs UVR well in the UVC and UVB spectral range. Keratinocytes of the skin (regardless of UVR exposure) are in a state of programmed apoptosis, during which the keratinocytes of the basal layer are removed from it and during the transition through all layers of the epidermis within 28 days turn into flakes of the outer stratum corneum, which are subsequently desquamated. It is clear that the keratinocyte response to UV exposure will depend on what phase of programmed apoptosis (at what distance from the basal layer) the keratinocyte experienced UV exposure, and this is the main reason for the difference of the UV effect for UVC and UVB on the skin. There are also differences in the initiation of mitochondrial (internal) and caspase-dependent (external) apoptosis for the UVC and UVB spectral ranges [9]. Sunburn cells (SBS) are the keratinocytes in the process of UV-induced apoptosis (both “pure” and pro-inflammatory). The appearance of SBC may be not associated with an inflammatory reaction, but the role of UV-induced apoptosis of skin keratinocytes in the development of UV erythema (hyperemia, redness) of the skin has been established, which allowed the development of a patent-protected METHOD FOR QUANTITATIVE ASSESSMENT OF APOPTOSIS SYSTEM [10], in which “the brightest lamp of skin display "(photoerythema) is used (as an indicator of the manifestation of strictly dosed sterile inflammation) to diagnose the state of the body systems involved in the elimination of UV-induced damage. Such systems (except apoptosis) include the immune system, the intracellular repair system, the microcirculation system and not only.

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<span class="mw-page-title-main">Ultraviolet</span> Form of electromagnetic radiation

Ultraviolet (UV) is a form of electromagnetic radiation with wavelength 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">7-Dehydrocholesterol</span> Chemical compound

7-Dehydrocholesterol (7-DHC) is a zoosterol that functions in the serum as a cholesterol precursor, and is photochemically converted to vitamin D3 in the skin, therefore functioning as provitamin-D3. The presence of this compound in human skin enables humans to manufacture vitamin D3 (cholecalciferol). Upon exposure to ultraviolet UV-B rays in the sun light, 7-DHC is converted into vitamin D3 via previtamin D3 as an intermediate isomer. It is also found in the milk of several mammalian species. Lanolin, a waxy substance that is naturally secreted by wool-bearing mammals, contains 7-DHC which is converted into vitamin D by sunlight and then ingested during grooming as a nutrient. In insects 7-dehydrocholesterol is a precursor for the hormone ecdysone, required for reaching adulthood. It was discovered by Nobel-laureate organic chemist Adolf Windaus.

<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. 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">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 be shed off, which happens every 40 to 56 days in humans.

<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 which can produce a tanning effect without exposure to ultraviolet radiation, known as sunless tanning.

<span class="mw-page-title-main">Indoor tanning</span> Tanning using an artificial source of ultraviolet light

Indoor tanning involves using a device that emits ultraviolet radiation to produce a cosmetic tan. Typically found in tanning salons, gyms, spas, hotels, and sporting facilities, and less often in private residences, the most common device is a horizontal tanning bed, also known as a sunbed or solarium. Vertical devices are known as tanning booths or stand-up sunbeds.

<span class="mw-page-title-main">Actinic keratosis</span> Skin disorder

Actinic keratosis (AK), sometimes called solar keratosis or senile keratosis, is a pre-cancerous area of thick, scaly, or crusty skin. Actinic keratosis is a disorder of epidermal keratinocytes that is induced by ultraviolet (UV) light exposure. These growths are more common in fair-skinned people and those who are frequently in the sun. They are believed to form when skin gets damaged by UV radiation from the sun or indoor tanning beds, usually over the course of decades. Given their pre-cancerous nature, if left untreated, they may turn into a type of skin cancer called squamous cell carcinoma. Untreated lesions have up to a 20% risk of progression to squamous cell carcinoma, so treatment by a dermatologist is recommended.

PUVA is an ultraviolet light therapy treatment for skin diseases: vitiligo, eczema, psoriasis, graft-versus-host disease, mycosis fungoides, large plaque parapsoriasis, and cutaneous T-cell lymphoma, using the sensitizing effects of the drug psoralen. The psoralen is applied or taken orally to sensitize the skin, then the skin is exposed to UVA.

<span class="mw-page-title-main">Ultraviolet index</span> Measurement of strength of sunburn-producing ultraviolet (UV) radiation

The ultraviolet index, or UV index, is an international standard measurement of the strength of the sunburn-producing ultraviolet (UV) radiation at a particular place and time. It is primarily used in daily and hourly forecasts aimed at the general public. The UV index is designed as an open-ended linear scale, directly proportional to the intensity of UV radiation, and adjusting for wavelength based on what causes human skin to sunburn. The purpose of the UV index is to help people effectively protect themselves from UV radiation, which has health benefits in moderation but in excess causes sunburn, skin aging, DNA damage, skin cancer, immunosuppression, and eye damage, such as cataracts.

<span class="mw-page-title-main">Radiation burn</span> Damage to skin or biological tissue from radiation exposure

A radiation burn is a damage to the skin or other biological tissue and organs as an effect of radiation. The radiation types of greatest concern are thermal radiation, radio frequency energy, ultraviolet light and ionizing radiation.

<span class="mw-page-title-main">Pyrimidine dimer</span> Type of damage to DNA

Pyrimidine dimers are molecular lesions formed from thymine or cytosine bases in DNA via photochemical reactions, commonly associated with direct DNA damage. Ultraviolet light induces the formation of covalent linkages between consecutive bases along the nucleotide chain in the vicinity of their carbon–carbon double bonds. The photo-coupled dimers are fluorescent. The dimerization reaction can also occur among pyrimidine bases in dsRNA —uracil or cytosine. Two common UV products are cyclobutane pyrimidine dimers (CPDs) and 6–4 photoproducts. These premutagenic lesions alter the structure of the DNA helix and cause non-canonical base pairing. Specifically, adjacent thymines or cytosines in DNA will form a cyclobutane ring when joined together and cause a distortion in the DNA. This distortion prevents replication or transcription machinery beyond the site of the dimerization. Up to 50–100 such reactions per second might occur in a skin cell during exposure to sunlight, but are usually corrected within seconds by photolyase reactivation or nucleotide excision repair. In humans, the most common form of DNA repair is nucleotide excision repair (NER). In contrast, organisms such as bacteria can counterintuitively harvest energy from the sun to fix DNA damage from pyrimidine dimers via photolyase activity. If these lesions are not fixed, polymerase machinery may misread or add in the incorrect nucleotide to the strand. If the damage to the DNA is overwhelming, mutations can arise within the genome of an organism and may lead to the production of cancer cells. Uncorrected lesions can inhibit polymerases, cause misreading during transcription or replication, or lead to arrest of replication. It causes sunburn and it triggers the production of melanin. Pyrimidine dimers are the primary cause of melanomas in humans.

<span class="mw-page-title-main">Human skin</span> Outer covering of the body

The human skin is the outer covering of the body and is the largest organ of the integumentary system. The skin has up to seven layers of ectodermal tissue guarding muscles, bones, ligaments and internal organs. Human skin is similar to most of the other mammals' skin, and it is very similar to pig skin. Though nearly all human skin is covered with hair follicles, it can appear hairless. There are two general types of skin, hairy and glabrous skin (hairless). The adjective cutaneous literally means "of the skin".

<span class="mw-page-title-main">Light skin</span> Human skin color

Light skin is a human skin color that has a base level of eumelanin pigmentation that has adapted to environments of low UV radiation. Light skin is most commonly found amongst the native populations of Europe, Central Asia, and Northeast Asia as measured through skin reflectance. People with light skin pigmentation are often referred to as "white" although these usages can be ambiguous in some countries where they are used to refer specifically to certain ethnic groups or populations.

UV-B lamps are lamps that emit a spectrum of ultraviolet light with wavelengths ranging from 290–320 nanometers. This spectrum is also commonly called the biological spectrum due to the human body's sensitivity to light of such a wavelength. UV-B light does not tan the skin very much, compared to the UV-A lamps that are used in tanning beds.

<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.

<span class="mw-page-title-main">Health effects of sunlight exposure</span>

Exposing skin to the ultraviolet radiation in sunlight has both positive and negative health effects. On the positive side, exposure allows for the synthesis of vitamin D3. Vitamin D has been suggested as having a wide range of positive health effects, which include strengthening bones and possibly inhibiting the growth of some cancers. A dietary supplement can also supply vitamin D, but there are also benefits to exposure not obtainable through Vitamin D supplementation. Long-term sun exposure is associated with reduced all-cause mortality and reduced mortality risk from cardiovascular disease (CVD), some forms of cancer, and non-CVD/noncancer related disease, with indications in these studies that Vitamin D is not the mediator. Supplementation offers limited bioavailability and no synthesis of subdermal nitric oxide. UV exposure also has positive effects for endorphin levels, and possibly for protection against multiple sclerosis. Abundant visible light to the eyes gives health benefits through its association with the timing of melatonin synthesis, maintenance of normal and robust circadian rhythms, and reduced risk of seasonal affective disorder.

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.

Animal-type melanoma is a rare subtype of melanoma that is characterized by heavily pigmented dermal epithelioid and spindled melanocytes. Animal-type melanoma is also known to be called equine-type melanoma, pigment synthesizing melanoma, and pigmented epithelioid melanocytoma (PEM). While melanoma is known as the most aggressive skin cancer, the mortality for PEM is lower than in other melanoma types. Animal-type melanoma earned its name due to the resemblance of melanocytic tumors in grey horses.

<span class="mw-page-title-main">Dark skin</span> Human skin color

Dark skin is a type of human skin color that is rich in melanin pigments. People with very dark skin are often referred to as "black people", although this usage can be ambiguous in some countries where it is also used to specifically refer to different ethnic groups or populations.

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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.

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.

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.

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]

References

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  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
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  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 (15): 6639–48. doi:10.1128/MCB.25.15.6639-6648.2005. PMC   1190357 . PMID   16024799.