Anti-aging Flashcards
UV damage to DNA results in
DNA repair/apoptosis
UV damage to keratinocytes results in
epidermal turnover due to cytokine production, growth and migration
Photoaged skin has extensive damage to
dermal connective tissue
UV irradiation induces expression of certain members of ____ family, which ______
MMP (matrix mellanoproteinase)
degrade collagen and other ECM proteins comprising dermal connective tissue
Major structural protein in dermal extracellular matrix
Collagen I
Dermal fibroblasts synthesize
Procollagen
2 primary pathways by which UV irradiation alters dermal collagen
- stimulation of collagen breakdown->fragment, disorganized collagen
- inhibition of procollagen synthesis–>loss of collagen content
Pathways that control procollagen expression
TGF-b
Collagen-degrading enyzmes ____ are produced in _____ and diffuse to _____, and this diffusion may be aided by
MMP-1, 3, 9
epidermis
dermis
direct binding of MMPs to collagenous ECM
Cells respond to excessive UV-induced damage via activation of
transcription factors
NF-Kappa B
AP-1
p53
Direct absorption of UVB photons leads to
- cyclobutane pyrimidine dimers
- pyrimidine (6-4) pyrimidone photoproduct
replication of damaged DNA –> mutations
UVB induced mutations
C->T, CC->TT at dyprimidine sites
UVA is most commonly associated with
oxidative damage
Main mutations of long wave UVA
G->T transversions
presumably arising through mechanisms involving oxidized DNA bases
main DNA product from UVA damage through oxidative mechanism
production of O2 singlet->8-oxo-guanine
Cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts alter the structure of DNA, and consequently,
inhibit polymerases
arrest replication
Dimers may be repaired by
photoreactivation
nucleotide excision repair
role of p53 gene
role of p53 transcription factor
tumor suppressor gene
major role in protection of cells from DNA damage
phosphoprotein regulates expression of stress response to genotoxic stress
genotoxic stress causes
p53 nucleoprotein accumulates, binds to DNA to activate transcription
p53 regulates cell cycle progression by
- arresting in late G1 (stimulates synthesis of inhibitors of cyclin-dependent kinases) to promote DNA repair
- triggering apoptosis
Most p53 mutations are in ____ domain, which causes
DBD (DNA-binding core domain)
it to be unable to bind to DNA, transcription of target genes that code repair factors prevented
Scientists propose MPF, which is
Mutation protection factor
ability of sunscreen to reduce DNA damage following UV exposure and attenuate epidermal expression of p53
critical event leading to activation of p53
phosphorylation of N-terminal domain
Protein kinases known to target transcriptional activation domain of p53
MAPK family
ATR/ATM/CHK1/CHK2/DNA-PK, CAK
Heart of the problem of UV induced immunosuppression
elevation of IL-10
Methods to attenuate signs/symptoms of photoaging
Retinoic acid
antioxidants
estrogens
growth factors/cytokines
mode of action of All Trans Retinoic Acid (tretinoin)
nuclear hormone receptor agonist
binds to nuclear transcription factors
Tretinoin facilitates _____ and stimulates ______ within _______ of sun exposed skin
ability to prevent collagen loss
stimulate new collagen formation
papillary dermis
RAR binds _____ and ____, RXR binds _____
RAR: RA and 9-cis RA
RXR: 9-cis RA
Retinoic acid receptors bind to _______ regions of DNA, therby initiating __________
hormone response elements
ligand-dependent gene transcription
