Rottlerin Reduces cAMP/CREB-Mediated Melanogenesis via Regulation of Autophagy

Nurinanda Prisky Qomaladewi1, Mi-Yeon Kim2, Jae Youl Cho3

  • 1Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea. prisky95@skku.edu.

Insights

Rottlerin, an autophagy inducer, inhibits melanoma cell melanin production by targeting the cyclic adenosine monophosphate (cAMP)/cAMP response element binding (CREB) pathway. This study clarifies autophagy

Area of Science:

  • Cell Biology
  • Biochemistry
  • Dermatology

Background:

  • Melanogenesis, melanin production by melanocytes, protects skin but is disrupted by radiation, leading to melanoma.
  • Cellular autophagy is being explored to stabilize melanogenesis in melanoma.
  • The precise role of autophagy in regulating melanogenesis within melanoma cells remains unclear.

Purpose of the Study:

  • To investigate the role of the cyclic adenosine monophosphate (cAMP)/cAMP response element binding (CREB) signaling pathway in melanogenesis.
  • To determine how autophagy influences melanogenesis in melanoma cells, using rottlerin as an autophagy inducer.

Main Methods:

  • Utilized rottlerin as an autophagy inducer in melanoma cell models.
  • Investigated the impact of rottlerin on the cAMP/CREB signaling pathway.
  • Assessed changes in melanin production in response to rottlerin treatment.

Main Results:

  • Rottlerin was found to inhibit melanin production in melanoma cells.
  • The inhibitory effect of rottlerin on melanin production is mediated by targeting the cAMP signaling pathway.
  • Rottlerin's action on cAMP was observed despite initial activation by alpha-melanocyte stimulating hormone (α-MSH).

Conclusions:

  • Rottlerin acts as a key autophagy inducer in regulating melanogenesis.
  • The cAMP/CREB signaling pathway is a critical target for rottlerin's effects on melanogenesis.
  • Findings provide insights into potential therapeutic strategies for melanoma by modulating autophagy and melanogenesis.

Related Concept Videos

Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
5.7K
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
8.8K
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
8.4K
Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
25.8K
Reducing Line Loss01:18

Reducing Line Loss

In a three-phase circuit, line loss is an indicator of energy dissipated as heat due to the resistance of transmission lines. To address this, incorporating transformers into the system—a step-up transformer at the source and a step-down transformer at the load—is a strategic solution. Two three-phase transformers are introduced to improve this.
With a step-up transformer at the source, the voltage is increased, thereby reducing the current in the transmission lines since power loss in...
372
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
33.5K