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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

A

XPC

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
Q

Melanocytes & Melanin production

A
  • In basal layer
  • Pheomelanin –> Eumelanin –> Mature melanin (as move outward from ER)
  • Tyrosinase is the rate-limiting step
26
Q

Genes that control pigmentation

A

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
Q

Pigment control – SLC24A5

A

= K-dependent Na/Ca ion exchanger

- Explains 225-38% of European / African differences in pigmentation

28
Q

Pigment control –SLC45A2

A

= aka MATP (Membrane Associated Transporter Protein)
= Marker for Caucasians
= Important in melanoma / nevi-formation

29
Q

Results of Mutations in Genes Controlling Pigmentation

A

Humans & Mice: Oculocutaneous Albinism

Mice: Agouti (expression of agouti-signaling protein)

30
Q

Oculocutaneous Albinism- Types & Enzyme involved

A

OCA I: Tyrosinase
OCA II: Pink
OCA III: Tyrp 1
OCA IV: MATP

31
Q

Racial Differences in Pigmentation

A
  • 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
Q

Melanosome & skin color

A

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
Q

Photocarcinogenesis Cascade

A

UV Exposure –> DNA damage –> Mutations –> Multistage Carcinogenesis (Initiation, Promotion, Transformation)

34
Q

UV-Induced Skin Cancers

A

Melanoma

Non-Melanoma Skin Cancer = Basal & Squamous Cell Carcinomas

35
Q

Photodermatoses – Types

A

Idiopathic (probably immunologic)
DNA repair defects
Chemical photosensitivity
Photoaggravated

36
Q

Photodermatoses – Idiopathic/immunologic

A

Solar urticaria, PMLE, actinic prurigo

37
Q

Photodermatoses – DNA repair defects

A

Xeroderma pigmentosum

38
Q

Photodermatoses – Chemical photosensitivity

A

Drug-induced

Porphyria (purpling, blisters, necrosis)

39
Q

Photodermatoses – Photoaggravated

A

Psoriasis

Atopic Dermatitis

40
Q

The Paradox of UV phototherapy

A

For treatment of

  • Extensive psoriasis
  • Atopic dermatitis
  • Cutaneous T cell lymphoma
  • Mastocytosis
  • Repigmentation of vitiligo
41
Q

SPF refers to…

A

only refers to UVB rating

42
Q

SPF & Other sunblocks

A

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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