Polydeoxyribonucleotide Activates Mitochondrial Biogenesis but Reduces MMP-1 Activity and Melanin Biosynthesis in Cultured Skin Cells
The regulation of mitochondrial biogenesis, melanogenesis, and connective tissue proteins is critical for homeostasis and aging skin cells. We examined the biological effects of polydeoxyribonucleotide (PDRN) on mitochondrial biogenesis, melanogenesis, and connective tissue proteins in vitro. In a r...
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| Veröffentlicht in: | Applied biochemistry and biotechnology 2020-06, Vol.191 (2), p.540-554 |
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| creator | Kim, Yeon-Ji Kim, Min-Jung Kweon, Dong-Keon Lim, Seung-Taik Lee, Sung-Joon |
| description | The regulation of mitochondrial biogenesis, melanogenesis, and connective tissue proteins is critical for homeostasis and aging skin cells. We examined the biological effects of polydeoxyribonucleotide (PDRN) on mitochondrial biogenesis, melanogenesis, and connective tissue proteins in vitro. In a radical scavenging assay, PDRN showed antioxidant activities in a dose-dependent manner, and those activities can suppress cellular oxidative stress in skin cells. PDRN directly inhibited mushroom tyrosinase activity and cellular tyrosinase activity, thus significantly reducing the cellular melanin content in B16-F10 melanocytes. The mRNA and protein expressions of the microphthalmia-associated transcription factor (MITF), which is a key melanogenic gene transcription factor, were significantly downregulated by PDRN. Accordingly, tyrosinase-related protein 1, dopachrome tautomerase, and tyrosinase, which gene expressions were regulated by MITF, were significantly downregulated by PDRN. Mitotracker-probed mitochondria image analysis suggested that PDRN enhanced mitochondrial density in both murine melanoma cells and in human skin fibroblast cells. In addition, PDRN strongly suppressed in vitro elastase enzyme activity in a dose-dependent manner and inhibited matrix metalloproteinase-1 gene expression in human skin fibroblast cells. Collectively, these findings indicate that PDRN has multiple beneficial biological activities in skin cells: hypopigmentation, induction of mitochondrial biogenesis, and the inhibition of collective tissue proteins. |
| doi_str_mv | 10.1007/s12010-019-03171-2 |
| format | Article |
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We examined the biological effects of polydeoxyribonucleotide (PDRN) on mitochondrial biogenesis, melanogenesis, and connective tissue proteins in vitro. In a radical scavenging assay, PDRN showed antioxidant activities in a dose-dependent manner, and those activities can suppress cellular oxidative stress in skin cells. PDRN directly inhibited mushroom tyrosinase activity and cellular tyrosinase activity, thus significantly reducing the cellular melanin content in B16-F10 melanocytes. The mRNA and protein expressions of the microphthalmia-associated transcription factor (MITF), which is a key melanogenic gene transcription factor, were significantly downregulated by PDRN. Accordingly, tyrosinase-related protein 1, dopachrome tautomerase, and tyrosinase, which gene expressions were regulated by MITF, were significantly downregulated by PDRN. Mitotracker-probed mitochondria image analysis suggested that PDRN enhanced mitochondrial density in both murine melanoma cells and in human skin fibroblast cells. In addition, PDRN strongly suppressed in vitro elastase enzyme activity in a dose-dependent manner and inhibited matrix metalloproteinase-1 gene expression in human skin fibroblast cells. Collectively, these findings indicate that PDRN has multiple beneficial biological activities in skin cells: hypopigmentation, induction of mitochondrial biogenesis, and the inhibition of collective tissue proteins.</description><identifier>ISSN: 0273-2289</identifier><identifier>EISSN: 1559-0291</identifier><identifier>DOI: 10.1007/s12010-019-03171-2</identifier><identifier>PMID: 31811642</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Aging ; Animals ; Antioxidants ; Biochemistry ; Biological effects ; Biosynthesis ; Biotechnology ; Cell Line ; Chemistry ; Chemistry and Materials Science ; Connective tissue ; Connective tissues ; Dopachrome isomerase ; Down-Regulation ; Elastase ; Enzymatic activity ; Enzyme activity ; Fibroblasts ; Gene expression ; Gene Expression Regulation - drug effects ; Homeostasis ; Humans ; Image analysis ; Image enhancement ; Image processing ; Interstitial collagenase ; Matrix metalloproteinase ; Matrix Metalloproteinase 1 - metabolism ; Matrix metalloproteinases ; Melanin ; Melanins - biosynthesis ; Melanins - genetics ; Melanocytes ; Melanoma ; Metalloproteinase ; Mice ; Microphthalmia-associated transcription factor ; Microphthalmia-Associated Transcription Factor - metabolism ; Mitochondria ; Mitochondria - drug effects ; Mushrooms ; Organelle Biogenesis ; Oxidative stress ; Oxidoreductases - metabolism ; Pigmentation ; Polydeoxyribonucleotides - pharmacology ; Proteins ; RNA, Messenger - metabolism ; Scavenging ; Skin ; Skin - metabolism ; Transcription factors ; Tyrosinase ; Tyrosinase-related protein 1</subject><ispartof>Applied biochemistry and biotechnology, 2020-06, Vol.191 (2), p.540-554</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2019</rights><rights>Springer Science+Business Media, LLC, part of Springer Nature 2019.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-b33fec657b4873704ffc4e60a5fed685c0fdee947b160e7ba5a82ea94a0b7a093</citedby><cites>FETCH-LOGICAL-c412t-b33fec657b4873704ffc4e60a5fed685c0fdee947b160e7ba5a82ea94a0b7a093</cites><orcidid>0000-0002-0661-5255</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12010-019-03171-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12010-019-03171-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31811642$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Yeon-Ji</creatorcontrib><creatorcontrib>Kim, Min-Jung</creatorcontrib><creatorcontrib>Kweon, Dong-Keon</creatorcontrib><creatorcontrib>Lim, Seung-Taik</creatorcontrib><creatorcontrib>Lee, Sung-Joon</creatorcontrib><title>Polydeoxyribonucleotide Activates Mitochondrial Biogenesis but Reduces MMP-1 Activity and Melanin Biosynthesis in Cultured Skin Cells</title><title>Applied biochemistry and biotechnology</title><addtitle>Appl Biochem Biotechnol</addtitle><addtitle>Appl Biochem Biotechnol</addtitle><description>The regulation of mitochondrial biogenesis, melanogenesis, and connective tissue proteins is critical for homeostasis and aging skin cells. We examined the biological effects of polydeoxyribonucleotide (PDRN) on mitochondrial biogenesis, melanogenesis, and connective tissue proteins in vitro. In a radical scavenging assay, PDRN showed antioxidant activities in a dose-dependent manner, and those activities can suppress cellular oxidative stress in skin cells. PDRN directly inhibited mushroom tyrosinase activity and cellular tyrosinase activity, thus significantly reducing the cellular melanin content in B16-F10 melanocytes. The mRNA and protein expressions of the microphthalmia-associated transcription factor (MITF), which is a key melanogenic gene transcription factor, were significantly downregulated by PDRN. Accordingly, tyrosinase-related protein 1, dopachrome tautomerase, and tyrosinase, which gene expressions were regulated by MITF, were significantly downregulated by PDRN. Mitotracker-probed mitochondria image analysis suggested that PDRN enhanced mitochondrial density in both murine melanoma cells and in human skin fibroblast cells. In addition, PDRN strongly suppressed in vitro elastase enzyme activity in a dose-dependent manner and inhibited matrix metalloproteinase-1 gene expression in human skin fibroblast cells. Collectively, these findings indicate that PDRN has multiple beneficial biological activities in skin cells: hypopigmentation, induction of mitochondrial biogenesis, and the inhibition of collective tissue proteins.</description><subject>Aging</subject><subject>Animals</subject><subject>Antioxidants</subject><subject>Biochemistry</subject><subject>Biological effects</subject><subject>Biosynthesis</subject><subject>Biotechnology</subject><subject>Cell Line</subject><subject>Chemistry</subject><subject>Chemistry and Materials Science</subject><subject>Connective tissue</subject><subject>Connective tissues</subject><subject>Dopachrome isomerase</subject><subject>Down-Regulation</subject><subject>Elastase</subject><subject>Enzymatic activity</subject><subject>Enzyme activity</subject><subject>Fibroblasts</subject><subject>Gene expression</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Image analysis</subject><subject>Image enhancement</subject><subject>Image processing</subject><subject>Interstitial collagenase</subject><subject>Matrix metalloproteinase</subject><subject>Matrix Metalloproteinase 1 - metabolism</subject><subject>Matrix metalloproteinases</subject><subject>Melanin</subject><subject>Melanins - biosynthesis</subject><subject>Melanins - genetics</subject><subject>Melanocytes</subject><subject>Melanoma</subject><subject>Metalloproteinase</subject><subject>Mice</subject><subject>Microphthalmia-associated transcription factor</subject><subject>Microphthalmia-Associated Transcription Factor - metabolism</subject><subject>Mitochondria</subject><subject>Mitochondria - drug effects</subject><subject>Mushrooms</subject><subject>Organelle Biogenesis</subject><subject>Oxidative stress</subject><subject>Oxidoreductases - metabolism</subject><subject>Pigmentation</subject><subject>Polydeoxyribonucleotides - pharmacology</subject><subject>Proteins</subject><subject>RNA, Messenger - metabolism</subject><subject>Scavenging</subject><subject>Skin</subject><subject>Skin - metabolism</subject><subject>Transcription factors</subject><subject>Tyrosinase</subject><subject>Tyrosinase-related protein 1</subject><issn>0273-2289</issn><issn>1559-0291</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kM1u1TAQhS0EopfCC7BAkVinzDhOnCzLVaFIvaLiZ2059qR1Se1iO4g8QN-7uU1pd6ysI3_njPQx9hbhCAHkh4QcEErAroQKJZb8GdtgXS-Rd_icbYDLquS87Q7Yq5SuAJC3tXzJDipsERvBN-z2PIyzpfB3jq4PfjIjhewsFccmuz86Uyp2LgdzGbyNTo_FRxcuyFNyqeinXHwjO5k9tDsvcS25PBfa22JHo_bO7xtp9vnyvrPk7TTmKZItvv_aJxrH9Jq9GPSY6M3De8h-fjr5sT0tz75-_rI9PiuNQJ7LvqoGMk0te9HKSoIYBiOoAV0PZJu2NjBYok7IHhsg2etat5x0JzT0UkNXHbL36-5NDL8nSlldhSn65aTiAhFqlKJZKL5SJoaUIg3qJrprHWeFoPbm1WpeLebVvXnFl9K7h-mpvyb7WPmnegGqFUjLl7-g-HT7P7N3Gm6QzA</recordid><startdate>20200601</startdate><enddate>20200601</enddate><creator>Kim, Yeon-Ji</creator><creator>Kim, Min-Jung</creator><creator>Kweon, Dong-Keon</creator><creator>Lim, Seung-Taik</creator><creator>Lee, Sung-Joon</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7ST</scope><scope>7T7</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>SOI</scope><orcidid>https://orcid.org/0000-0002-0661-5255</orcidid></search><sort><creationdate>20200601</creationdate><title>Polydeoxyribonucleotide Activates Mitochondrial Biogenesis but Reduces MMP-1 Activity and Melanin Biosynthesis in Cultured Skin Cells</title><author>Kim, Yeon-Ji ; Kim, Min-Jung ; Kweon, Dong-Keon ; Lim, Seung-Taik ; Lee, Sung-Joon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-b33fec657b4873704ffc4e60a5fed685c0fdee947b160e7ba5a82ea94a0b7a093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Aging</topic><topic>Animals</topic><topic>Antioxidants</topic><topic>Biochemistry</topic><topic>Biological effects</topic><topic>Biosynthesis</topic><topic>Biotechnology</topic><topic>Cell Line</topic><topic>Chemistry</topic><topic>Chemistry and Materials Science</topic><topic>Connective tissue</topic><topic>Connective tissues</topic><topic>Dopachrome isomerase</topic><topic>Down-Regulation</topic><topic>Elastase</topic><topic>Enzymatic activity</topic><topic>Enzyme activity</topic><topic>Fibroblasts</topic><topic>Gene expression</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Image analysis</topic><topic>Image enhancement</topic><topic>Image processing</topic><topic>Interstitial collagenase</topic><topic>Matrix metalloproteinase</topic><topic>Matrix Metalloproteinase 1 - metabolism</topic><topic>Matrix metalloproteinases</topic><topic>Melanin</topic><topic>Melanins - biosynthesis</topic><topic>Melanins - genetics</topic><topic>Melanocytes</topic><topic>Melanoma</topic><topic>Metalloproteinase</topic><topic>Mice</topic><topic>Microphthalmia-associated transcription factor</topic><topic>Microphthalmia-Associated Transcription Factor - metabolism</topic><topic>Mitochondria</topic><topic>Mitochondria - drug effects</topic><topic>Mushrooms</topic><topic>Organelle Biogenesis</topic><topic>Oxidative stress</topic><topic>Oxidoreductases - metabolism</topic><topic>Pigmentation</topic><topic>Polydeoxyribonucleotides - pharmacology</topic><topic>Proteins</topic><topic>RNA, Messenger - metabolism</topic><topic>Scavenging</topic><topic>Skin</topic><topic>Skin - metabolism</topic><topic>Transcription factors</topic><topic>Tyrosinase</topic><topic>Tyrosinase-related protein 1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Yeon-Ji</creatorcontrib><creatorcontrib>Kim, Min-Jung</creatorcontrib><creatorcontrib>Kweon, Dong-Keon</creatorcontrib><creatorcontrib>Lim, Seung-Taik</creatorcontrib><creatorcontrib>Lee, Sung-Joon</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Environment Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>Environment Abstracts</collection><jtitle>Applied biochemistry and biotechnology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Yeon-Ji</au><au>Kim, Min-Jung</au><au>Kweon, Dong-Keon</au><au>Lim, Seung-Taik</au><au>Lee, Sung-Joon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Polydeoxyribonucleotide Activates Mitochondrial Biogenesis but Reduces MMP-1 Activity and Melanin Biosynthesis in Cultured Skin Cells</atitle><jtitle>Applied biochemistry and biotechnology</jtitle><stitle>Appl Biochem Biotechnol</stitle><addtitle>Appl Biochem Biotechnol</addtitle><date>2020-06-01</date><risdate>2020</risdate><volume>191</volume><issue>2</issue><spage>540</spage><epage>554</epage><pages>540-554</pages><issn>0273-2289</issn><eissn>1559-0291</eissn><abstract>The regulation of mitochondrial biogenesis, melanogenesis, and connective tissue proteins is critical for homeostasis and aging skin cells. We examined the biological effects of polydeoxyribonucleotide (PDRN) on mitochondrial biogenesis, melanogenesis, and connective tissue proteins in vitro. In a radical scavenging assay, PDRN showed antioxidant activities in a dose-dependent manner, and those activities can suppress cellular oxidative stress in skin cells. PDRN directly inhibited mushroom tyrosinase activity and cellular tyrosinase activity, thus significantly reducing the cellular melanin content in B16-F10 melanocytes. The mRNA and protein expressions of the microphthalmia-associated transcription factor (MITF), which is a key melanogenic gene transcription factor, were significantly downregulated by PDRN. Accordingly, tyrosinase-related protein 1, dopachrome tautomerase, and tyrosinase, which gene expressions were regulated by MITF, were significantly downregulated by PDRN. Mitotracker-probed mitochondria image analysis suggested that PDRN enhanced mitochondrial density in both murine melanoma cells and in human skin fibroblast cells. In addition, PDRN strongly suppressed in vitro elastase enzyme activity in a dose-dependent manner and inhibited matrix metalloproteinase-1 gene expression in human skin fibroblast cells. Collectively, these findings indicate that PDRN has multiple beneficial biological activities in skin cells: hypopigmentation, induction of mitochondrial biogenesis, and the inhibition of collective tissue proteins.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>31811642</pmid><doi>10.1007/s12010-019-03171-2</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-0661-5255</orcidid></addata></record> |
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| subjects | Aging Animals Antioxidants Biochemistry Biological effects Biosynthesis Biotechnology Cell Line Chemistry Chemistry and Materials Science Connective tissue Connective tissues Dopachrome isomerase Down-Regulation Elastase Enzymatic activity Enzyme activity Fibroblasts Gene expression Gene Expression Regulation - drug effects Homeostasis Humans Image analysis Image enhancement Image processing Interstitial collagenase Matrix metalloproteinase Matrix Metalloproteinase 1 - metabolism Matrix metalloproteinases Melanin Melanins - biosynthesis Melanins - genetics Melanocytes Melanoma Metalloproteinase Mice Microphthalmia-associated transcription factor Microphthalmia-Associated Transcription Factor - metabolism Mitochondria Mitochondria - drug effects Mushrooms Organelle Biogenesis Oxidative stress Oxidoreductases - metabolism Pigmentation Polydeoxyribonucleotides - pharmacology Proteins RNA, Messenger - metabolism Scavenging Skin Skin - metabolism Transcription factors Tyrosinase Tyrosinase-related protein 1 |
| title | Polydeoxyribonucleotide Activates Mitochondrial Biogenesis but Reduces MMP-1 Activity and Melanin Biosynthesis in Cultured Skin Cells |
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