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- Title
Nalfurafine Hydrochloride, a κ-Opioid Receptor Agonist, Induces Melanophagy via PKA Inhibition in B16F1 Cells.
- Authors
Lee, Ha Jung; Kim, Seong Hyun; Kim, Yong Hwan; Kim, So Hyun; Oh, Gyeong Seok; Bae, Ji-Eun; Kim, Joon Bum; Park, Na Yeon; Park, Kyuhee; Yeom, Eunbyul; Jeong, Kwiwan; Kim, Pansoo; Jo, Doo Sin; Cho, Dong-Hyung
- Abstract
Selective autophagy controls cellular homeostasis by degrading unnecessary or damaged cellular components. Melanosomes are specialized organelles that regulate the biogenesis, storage, and transport of melanin in melanocytes. However, the mechanisms underlying melanosomal autophagy, known as the melanophagy pathway, are poorly understood. To better understand the mechanism of melanophagy, we screened an endocrine-hormone chemical library and identified nalfurafine hydrochlorides, a κ-opioid receptor agonist, as a potent inducer of melanophagy. Treatment with nalfurafine hydrochloride increased autophagy and reduced melanin content in alpha-melanocyte-stimulating hormone (α-MSH)-treated cells. Furthermore, inhibition of autophagy blocked melanosomal degradation and reversed the nalfurafine hydrochloride-induced decrease in melanin content in α-MSH-treated cells. Consistently, treatment with other κ-opioid receptor agonists, such as MCOPPB or mianserin, inhibited excessive melanin production but induced autophagy in B16F1 cells. Furthermore, nalfurafine hydrochloride inhibited protein kinase A (PKA) activation, which was notably restored by forskolin, a PKA activator. Additionally, forskolin treatment further suppressed melanosomal degradation as well as the anti-pigmentation activity of nalfurafine hydrochloride in α-MSH-treated cells. Collectively, our data suggest that stimulation of κ-opioid receptors induces melanophagy by inhibiting PKA activation in α-MSH-treated B16F1 cells.
- Subjects
OPIOID receptors; CELL anatomy; CHEMICAL libraries; PROTEIN kinases; FORSKOLIN; MELANINS
- Publication
Cells (2073-4409), 2023, Vol 12, Issue 1, p146
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells12010146