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Alpha-melanocyte stimulating hormone-induced pigmentation is blocked by depletion of protein kinase C
H Y Park1, V Russakovsky, Y Ao
1Department of Dermatology, Boston University School of Medicine, Massachusetts 02118, USA. HYPark@acs.bu.edu
Abstract:
We have explored the role of protein kinase C (PKC) in pigmentation induced by alpha-melanocyte stimulating hormone (alpha-MSH). Using the well-studied S91 Cloudman mouse melanoma model system in which 10(-7) M alpha-MSH is known to produce a time-dependent increase in pigmentation, we found an increase in the activity of tyrosinase, the key enzyme in pigmentation, between Days 2 and 6 accompanied by an increase in mRNA and protein levels of tyrosinase, as well as an increase in the level of specifically the beta isoform of PKC. When S91 cells were treated with phorbol dibutyrate, 95% of PKC activity was lost within 48 h and the alpha-MSH-induced melanogenesis was completely blocked, as was the induction of tyrosinase mRNA and protein. Serially passaged S91 cells no longer capable of responding to alpha-MSH had an undetectable level of PKC-beta, although the tyrosinase protein level was identical to that of alpha-MSH-responsive cells. Furthermore, in these S91 cells alpha-MSH also did not increase the level of tyrosinase mRNA. Thus, induction of murine melanogenesis by alpha-MSH involves up-regulation of tyrosinase mRNA and protein mediated in part by the PKC-dependent pathway, associated with an up-regulation of the beta isoform previously demonstrated to specifically activate tyrosinase in human melanocytes.
Insights
Protein Kinase C (PKC) activation is crucial for alpha-melanocyte stimulating hormone (alpha-MSH) to induce pigmentation. This pathway up-regulates tyrosinase mRNA and protein, key for melanogenesis.
Area of Science:
- Cell Biology
- Biochemistry
- Dermatology
Background:
- Pigmentation is regulated by complex signaling pathways.
- Alpha-melanocyte stimulating hormone (alpha-MSH) is a key regulator of melanogenesis.
- Protein Kinase C (PKC) is implicated in various cellular processes.
Purpose of the Study:
- To investigate the role of PKC in alpha-MSH-induced pigmentation.
- To elucidate the molecular mechanisms linking alpha-MSH to melanogenesis.
- To identify specific PKC isoforms involved in this process.
Main Methods:
- Utilized the S91 Cloudman mouse melanoma model.
- Measured tyrosinase activity, mRNA, and protein levels.
- Assessed PKC activity and isoform levels following alpha-MSH and phorbol dibutyrate treatment.
Main Results:
- Alpha-MSH increased tyrosinase activity, mRNA, and protein, correlating with increased PKC-beta levels.
- Inhibition of PKC activity blocked alpha-MSH-induced melanogenesis and tyrosinase induction.
- Non-responsive S91 cells lacked detectable PKC-beta and did not up-regulate tyrosinase mRNA in response to alpha-MSH.
Conclusions:
- The PKC-dependent pathway, specifically involving PKC-beta, mediates alpha-MSH-induced up-regulation of tyrosinase mRNA and protein.
- PKC activation is essential for alpha-MSH to stimulate melanogenesis in this mouse melanoma model.
- Findings highlight the critical role of PKC-beta in regulating pigmentation.