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<130907 김준섭>
▶Objective : To know relation bewteen
HMG-CoA reductase and melanogensis
INHA University -
Bioengineering
ABSTRACT
 cholesterol  regulation of melanogenesis
 artemisinic acid  melanogenesis in human epidermal melanocyte
MITF
tyrosinase
TRP-1
TRP-2
•c-KIT, stem cell factor
•macrophage migration
inhibition factor(MIF)
•cAMP
•protein kinase activity
artemisinic acid  inhibition of C/EBP α  inhibition of HMG CoA reductase
INHA University -
Bioengineering
INTRODUCTION
 Cholesterol is an essential mammalian membrane protein
•cell integrity
•cell signaling
•cell metabolism
•membrane fluidity
•steroid hormone synthesis
 Cellular changes in endogenous synthesis and exogenous supply of
cholesterol occur through feedback regulation of HMG CoA reductase and
the low-density lipoprotein receptor(LPLR).
•sterol-response element (SRE)
•Sp1
•NF-Y
•a cyclic AMP-response element (CRE)
•C/EBP family binding element
Several important
elements of HMG CoA
reductase promoter
INHA University -
Bioengineering
MATERIALS AND METHODS
• Cell culture : human epidermal melanocyte
• Melanin content assay
• Histochemistry of reconstructed epidermis
• Cyclic AMP immunoassay
• Cell viability assay : MTT
• Real-time RT-PCR analysis
• HMG CoA reductase assay
• Western blot analysis
• Protein kinase A (PKA) activity assay
• Cholesterol content assay
INHA University -
Bioengineering
RESULTS
Fig. 1. Artemisinic acid inhibits melanogenesis in human epidermal melanocytes.
3.1. Artemisinic acid inhibits melanogenesis in human epidermal melanocytes
 Inhibitory effects of
artemisinic acid on
melanin formation were
found.
 Cytotoxic effects
were not observed (data
not shown)
 Reduction of
melanogenic protein
mRNA
INHA University -
Bioengineering
RESULTS
3.2. Cyclic AMP-PKA signaling was inhibited by artemisinic acid
 Levels of cAMP decreased significantly by treatment with artemisinic acid.
 A significant decrease in PKA activity was observed.
Fig. 2. Artemisinic acid reduces cAMP production and PKA activity.
INHA University -
Bioengineering
RESULTS
Fig. 3. Artemisinic acid inhibits cholesterol synthesis by downregulating the hydroxymethylglutaryl
CoA (HMG CoA) reductase gene.
3.3. Artemisinic acid inhibited cholesterol synthesis by downregulating the
hydroxymethylglutaryl CoA (HMG CoA) reductase gene
 Cholesterol content
decreased significantly
by artemisinic acid
treatment.
 Expression of HMG
CoA reductase, a
critical factor in
cholesterol synthesis,
decreased following
artemisinic acid
treatment
INHA University -
Bioengineering
RESULTS
3.4. Reduced expression of the HMG CoA reductase gene by artemisinic acid is
mediated through C/EBP α gene downregulation
Fig. 4. Reduced expression of the HMG CoA reductase gene by artemisinic acid is mediated by
downregulation of the C/EBP a gene.
artemisinic acid treatment  C/EBP a gene downregulation
INHA University -
Bioengineering
DISCUSSION
 Artemisinic acid downregulated HMG CoA reductase gene expression by
inhibiting C/EBP a gene expression, after which it reduced cholesterol
synthesis, consequently inhibiting melanogenesis
Fig. 5. Mechanisms of artemisinic acid-induced attenuation of melanogenesis.

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130907 paper study 준섭

  • 1. <130907 김준섭> ▶Objective : To know relation bewteen HMG-CoA reductase and melanogensis
  • 2. INHA University - Bioengineering ABSTRACT  cholesterol  regulation of melanogenesis  artemisinic acid  melanogenesis in human epidermal melanocyte MITF tyrosinase TRP-1 TRP-2 •c-KIT, stem cell factor •macrophage migration inhibition factor(MIF) •cAMP •protein kinase activity artemisinic acid  inhibition of C/EBP α  inhibition of HMG CoA reductase
  • 3. INHA University - Bioengineering INTRODUCTION  Cholesterol is an essential mammalian membrane protein •cell integrity •cell signaling •cell metabolism •membrane fluidity •steroid hormone synthesis  Cellular changes in endogenous synthesis and exogenous supply of cholesterol occur through feedback regulation of HMG CoA reductase and the low-density lipoprotein receptor(LPLR). •sterol-response element (SRE) •Sp1 •NF-Y •a cyclic AMP-response element (CRE) •C/EBP family binding element Several important elements of HMG CoA reductase promoter
  • 4. INHA University - Bioengineering MATERIALS AND METHODS • Cell culture : human epidermal melanocyte • Melanin content assay • Histochemistry of reconstructed epidermis • Cyclic AMP immunoassay • Cell viability assay : MTT • Real-time RT-PCR analysis • HMG CoA reductase assay • Western blot analysis • Protein kinase A (PKA) activity assay • Cholesterol content assay
  • 5. INHA University - Bioengineering RESULTS Fig. 1. Artemisinic acid inhibits melanogenesis in human epidermal melanocytes. 3.1. Artemisinic acid inhibits melanogenesis in human epidermal melanocytes  Inhibitory effects of artemisinic acid on melanin formation were found.  Cytotoxic effects were not observed (data not shown)  Reduction of melanogenic protein mRNA
  • 6. INHA University - Bioengineering RESULTS 3.2. Cyclic AMP-PKA signaling was inhibited by artemisinic acid  Levels of cAMP decreased significantly by treatment with artemisinic acid.  A significant decrease in PKA activity was observed. Fig. 2. Artemisinic acid reduces cAMP production and PKA activity.
  • 7. INHA University - Bioengineering RESULTS Fig. 3. Artemisinic acid inhibits cholesterol synthesis by downregulating the hydroxymethylglutaryl CoA (HMG CoA) reductase gene. 3.3. Artemisinic acid inhibited cholesterol synthesis by downregulating the hydroxymethylglutaryl CoA (HMG CoA) reductase gene  Cholesterol content decreased significantly by artemisinic acid treatment.  Expression of HMG CoA reductase, a critical factor in cholesterol synthesis, decreased following artemisinic acid treatment
  • 8. INHA University - Bioengineering RESULTS 3.4. Reduced expression of the HMG CoA reductase gene by artemisinic acid is mediated through C/EBP α gene downregulation Fig. 4. Reduced expression of the HMG CoA reductase gene by artemisinic acid is mediated by downregulation of the C/EBP a gene. artemisinic acid treatment  C/EBP a gene downregulation
  • 9. INHA University - Bioengineering DISCUSSION  Artemisinic acid downregulated HMG CoA reductase gene expression by inhibiting C/EBP a gene expression, after which it reduced cholesterol synthesis, consequently inhibiting melanogenesis Fig. 5. Mechanisms of artemisinic acid-induced attenuation of melanogenesis.

Editor's Notes

  1. melanin과 다른 organic compound와 비교를 하였다.
  2. melanin과 다른 organic compound와 비교를 하였다.
  3. melanin과 다른 organic compound와 비교를 하였다.
  4. melanin과 다른 organic compound와 비교를 하였다.
  5. melanin과 다른 organic compound와 비교를 하였다.
  6. melanin과 다른 organic compound와 비교를 하였다.