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Unit 3 D&D > DD 03-10-14 08-09am UV Light and Skin Repair - Box > Flashcards

DD 03-10-14 08-09am UV Light and Skin Repair - Box Flashcards

1
Q

UV Radiation - Effects on the Skin

A 
Damage to DNA, RNA, Lipids, Proteins
Both Pro-inflammatory & Immunosuppressive
Induction of Innate defenses
Induction of apoptosis 
Vitamin D synthesis
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2
Q

UV radiation & Vitamin D production

A

UVR induces the non-enzymatic synthesis of cholecalciferol (VitD3) and ergocalciferol (VitD2)

In liver & kidney, both are converted to systemically active form (Di-hydroxy VitD3)

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3
Q

Vitamin D from other sources

A

VitD3 & VitD2 are contained in dietary supplements

- But, there is controversy regarding VitD & cancer protection, and the need for UV-induced VitD

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4
Q

DNA damage by UVR

A 
Thymine dimer (cyclobutane pyrimidine dimer) : UVB
Pyrimidine-6-4 pyrimidone : UVB
Hydroxyguanosine : UVA & singlet oxygen
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5
Q

Outcomes of DNA Damage

A

Repair of damage
Apoptosis (p53-induced –> peeling in sunburn)
Gene mutation (carcinogenesis – initiation, transformation, progression)

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6
Q

Important mediators released by UVR – Primary Cytokines (primary responders to UV)

A

IL-1a, TNFalpha

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7
Q

Important mediators released by UVR – Secondary Cytokines

A

IL-6, -8, -10

GM-CSF

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8
Q

Important mediators released by UVR – Lipid Mediators

A

PAF, PGE2, LTB4

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9
Q

Important mediators released by UVR – Growth Factors & Tumor Progression Factors

A

MSH, ET-1, VEGF, MIA

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10
Q

Important mediators released by UVR – Mast Cell Mediators

A

Histamine

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11
Q

Proinflammatory effects of UVR – Mediators

A

Primary & Secondary cytokines and Lipid Mediators

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12
Q

Proinflammatory effects of UVR – Effects

A
  • Erythema
  • Sunburn cells
  • Potentiation of other types of cutaneous inflammation (adhesion molecule induction, cytokine/chemokine release)
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13
Q

Immunosuppressive effects of UVR - Effects

A
  • Decreased Langerhans cells (migration out of epidermis)
  • Induction of inhibitory cytokines (IL-10, Th2 cytokines)
  • Suppressor cells (Treg, NKT cells)  tolerance
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14
Q

UVR Immunosuppression cascade

A

UVR induces keratinocyte release of PAF & Cis-UCA

IL-10 is produced when…

  • Cis-UCA activates mast cells or B cells
  • PAF induces PGE2, which activates B cells

IL-10 blocks IL-12 production by DCs

T cells CANNOT be activated to form cytotoxic cells, but NKT & Treg induce tolerance

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15
Q

Melanin & UVR Immunosuppression

A

Melanin screens out a lot of the effects of UVR, but Immunosuppression is NOT inhibited by high melanin content (dark skin color)
–> potentiates induction of Non-melanoma skin cancer (NMSC)

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16
Q

Skin defenses against UVR

A

DNA repair
Apoptosis of cells w/DNA damage
Defenses against ROS
Melanin

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17
Q

Xerderma Pigmentosum

A

Family of disease with genetic defects in DNA Repair

–> premature skin aging & fatal UVR-induced skin cancers

18
Q

DNA Repair Enzyme involved in Nucleotide Excision repair

A

Excision of mutated strand of DNA <– DNA Ligase

19
Q

DNA Repair Enzyme for DNA damage recognition

20
Q

Repair Enzymes for Unwinding of DNA helix

A

XPA, XPB, XPD

21
Q

DNA Repair Enzymes for Incisions & Release of nucleotides

A

XPB, XPD, XPF, XPG

22
Q

DNA Repair Enzymes for Gap Filling & Ligation

A

PCNA, DNA Polymerase, RPA

23
Q

Activation of DNA Repair Enzymes

A

By UVR activation of p53

24
Q

Enzymes for Defense against Reactive Oxygens in the Epidermis

A

Peroxidases & Catalases
Superoxide dismutase
Glutathione reductase
Thioredoxin reductase

25
Melanocytes & Melanin production
- In basal layer - Pheomelanin --> Eumelanin --> Mature melanin (as move outward from ER) - Tyrosinase is the rate-limiting step
26
Genes that control pigmentation
Tyrosinase = Rate limiting, Oculocutaneous Albinism (OCA) TRP-1 & -2 (Tyrosinase-related) = Eumelanin Pink = transport (membrane protein) Silver = matrix protein MC1-R Tyr, Tyrp-1 & -2, ASP = Eumelanin vs. Pheomelanin
27
Pigment control – SLC24A5
= K-dependent Na/Ca ion exchanger | - Explains 225-38% of European / African differences in pigmentation
28
Pigment control –SLC45A2
= aka MATP (Membrane Associated Transporter Protein) = Marker for Caucasians = Important in melanoma / nevi-formation
29
Results of Mutations in Genes Controlling Pigmentation
Humans & Mice: Oculocutaneous Albinism Mice: Agouti (expression of agouti-signaling protein)
30
Oculocutaneous Albinism- Types & Enzyme involved
OCA I: Tyrosinase OCA II: Pink OCA III: Tyrp 1 OCA IV: MATP
31
Racial Differences in Pigmentation
- Difference melanosomal structure, distribution, & synthesis of melanin - Differences in MC1R, ASP, SLC transporters - Potential differences in signaling pathways that contol MITF: MSH, WNT, SCF/Kit
32
Melanosome & skin color
Not the number of melanocytes but rather, the deposition of melanosomes & the type of pigment produced by them Europeans – deposited in membrane-bound clusters Asians – produce more melanin, but looks like Europeans in depositions (clusters) Africans – larger, more mature melanosomes deposited individually throughout cell
33
Photocarcinogenesis Cascade
UV Exposure --> DNA damage --> Mutations --> Multistage Carcinogenesis (Initiation, Promotion, Transformation)
34
UV-Induced Skin Cancers
Melanoma Non-Melanoma Skin Cancer = Basal & Squamous Cell Carcinomas
35
Photodermatoses – Types
Idiopathic (probably immunologic) DNA repair defects Chemical photosensitivity Photoaggravated
36
Photodermatoses – Idiopathic/immunologic
Solar urticaria, PMLE, actinic prurigo
37
Photodermatoses – DNA repair defects
Xeroderma pigmentosum
38
Photodermatoses – Chemical photosensitivity
Drug-induced | Porphyria (purpling, blisters, necrosis)
39
Photodermatoses – Photoaggravated
Psoriasis | Atopic Dermatitis
40
The Paradox of UV phototherapy
For treatment of - Extensive psoriasis - Atopic dermatitis - Cutaneous T cell lymphoma - Mastocytosis - Repigmentation of vitiligo
41
SPF refers to...
only refers to UVB rating
42
SPF & Other sunblocks
Best sunscreens have both UVB & UVA protection - Parsol 1789, avobenzome - Neutrogena Helioplex - Nex gen: Mexoryl Unlike FDA says, sunscreen w/ SPF>15 is needed, esp. for photosensitive pts, skiers, pts w/cancer risk

Unit 3 D&D (18 decks)

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