Nalfurafine Hydrochloride, a κ-Opioid Receptor Agonist, Induces Melanophagy via PKA Inhibition in B16F1 Cells
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 mel...
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MDPI AG
2022-12-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/1/146 |
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| author | Ha Jung Lee Seong Hyun Kim Yong Hwan Kim So Hyun Kim Gyeong Seok Oh Ji-Eun Bae Joon Bum Kim Na Yeon Park Kyuhee Park Eunbyul Yeom Kwiwan Jeong Pansoo Kim Doo Sin Jo Dong-Hyung Cho |
| author_facet | Ha Jung Lee Seong Hyun Kim Yong Hwan Kim So Hyun Kim Gyeong Seok Oh Ji-Eun Bae Joon Bum Kim Na Yeon Park Kyuhee Park Eunbyul Yeom Kwiwan Jeong Pansoo Kim Doo Sin Jo Dong-Hyung Cho |
| author_sort | Ha Jung Lee |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T10:04:57Z |
| format | Article |
| id | doaj.art-722f57593fef48e08927f4a108909867 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T10:04:57Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-722f57593fef48e08927f4a1089098672023-11-16T15:06:42ZengMDPI AGCells2073-44092022-12-0112114610.3390/cells12010146Nalfurafine Hydrochloride, a κ-Opioid Receptor Agonist, Induces Melanophagy via PKA Inhibition in B16F1 CellsHa Jung Lee0Seong Hyun Kim1Yong Hwan Kim2So Hyun Kim3Gyeong Seok Oh4Ji-Eun Bae5Joon Bum Kim6Na Yeon Park7Kyuhee Park8Eunbyul Yeom9Kwiwan Jeong10Pansoo Kim11Doo Sin Jo12Dong-Hyung Cho13BK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, Republic of KoreaBK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, Republic of KoreaBK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, Republic of KoreaBK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, Republic of KoreaBK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, Republic of KoreaBrain Science and Engineering Institute, Kyungpook National University, Daegu 41566, Republic of KoreaBK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, Republic of KoreaBK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, Republic of KoreaBio-center, Gyeonggido Business & Science Accelerator, Gyeonggido, Suwon 16229, Republic of KoreaBK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, Republic of KoreaBio-center, Gyeonggido Business & Science Accelerator, Gyeonggido, Suwon 16229, Republic of KoreaBio-center, Gyeonggido Business & Science Accelerator, Gyeonggido, Suwon 16229, Republic of KoreaBK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, Republic of KoreaBK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, Republic of KoreaSelective 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.https://www.mdpi.com/2073-4409/12/1/146nalfurafine hydrochlorideautophagyκ-opioid receptormelanophagyB16F1 cells |
| spellingShingle | Ha Jung Lee Seong Hyun Kim Yong Hwan Kim So Hyun Kim Gyeong Seok Oh Ji-Eun Bae Joon Bum Kim Na Yeon Park Kyuhee Park Eunbyul Yeom Kwiwan Jeong Pansoo Kim Doo Sin Jo Dong-Hyung Cho Nalfurafine Hydrochloride, a κ-Opioid Receptor Agonist, Induces Melanophagy via PKA Inhibition in B16F1 Cells Cells nalfurafine hydrochloride autophagy κ-opioid receptor melanophagy B16F1 cells |
| title | Nalfurafine Hydrochloride, a κ-Opioid Receptor Agonist, Induces Melanophagy via PKA Inhibition in B16F1 Cells |
| title_full | Nalfurafine Hydrochloride, a κ-Opioid Receptor Agonist, Induces Melanophagy via PKA Inhibition in B16F1 Cells |
| title_fullStr | Nalfurafine Hydrochloride, a κ-Opioid Receptor Agonist, Induces Melanophagy via PKA Inhibition in B16F1 Cells |
| title_full_unstemmed | Nalfurafine Hydrochloride, a κ-Opioid Receptor Agonist, Induces Melanophagy via PKA Inhibition in B16F1 Cells |
| title_short | Nalfurafine Hydrochloride, a κ-Opioid Receptor Agonist, Induces Melanophagy via PKA Inhibition in B16F1 Cells |
| title_sort | nalfurafine hydrochloride a κ opioid receptor agonist induces melanophagy via pka inhibition in b16f1 cells |
| topic | nalfurafine hydrochloride autophagy κ-opioid receptor melanophagy B16F1 cells |
| url | https://www.mdpi.com/2073-4409/12/1/146 |
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