Sericin-Induced Melanogenesis in Cultured Retinal Pigment Epithelial Cells Is Associated with Elevated Levels of Hydrogen Peroxide and Inflammatory Proteins
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Cell Culture
2.3. In-Solution Digestion and Nano LC-Q Exactive Orbitrap Mass Spectrometry
2.4. Data Analysis
2.5. Immunoblotting
2.6. Light Microscopy
2.7. Scanning Electron Microscopy
2.8. Immunofluorescence
2.9. Viability Assay
2.10. Measurement of Superoxide and Hydrogen Peroxide Reactive Oxygen Species
2.11. Quantification of Pigmentation
2.12. Quantification of Microvilli
3. Results
3.1. Effects of Sericin on Protein Expression
3.2. Immunofluorescence and Immunoblotting
3.3. Sericin Increases Viability Despite Inducing an Inflammatory Response
3.4. Sericin Promotes Pigmentation of Cultured Human Retinal Pigment Epithelial Cells
3.5. Effects of Sericin on Superoxide Dismutase Substrate and Product
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are not available from the authors. |
Protein Name | Gene Symbol | FC | p-Value |
---|---|---|---|
Hydroxyacylglutathione hydrolase, mitochondrial | HAGH | 15.376 | 0.039 |
Low-density lipoprotein receptor | LDLR | 13.523 | 0.003 |
(Pyruvate dehydrogenase (acetyl-transferring))-phosphatase 1, mitochondrial | PDP1 | 12.853 | 0.010 |
Receptor-type tyrosine-protein phosphatase F | PTPRF | 11.652 | 0.030 |
Laminin subunit β-2 | LAMB2 | 10.453 | 0.001 |
Translational activator GCN1 | GCN1L1 | 9.168 | 0.003 |
Kinesin-like protein KIF1A | KIF1A | 9.129 | 0.029 |
Neural cell adhesion molecule L1 | L1CAM | 9.129 | 0.029 |
Protein FAM134C | FAM134C | 8.789 | 0.009 |
Pyridoxine-5′-phosphate oxidase | PNPO | 8.789 | 0.009 |
Hsc70-interacting protein | ST13 | 7.696 | 0.039 |
Protein CYR61 | CYR61 | 7.346 | 0.020 |
Isocitrate dehydrogenase (NAD) subunit α, mitochondrial | IDH3A | 6.797 | 0.047 |
Leucine-rich repeat neuronal protein 1 | LRRN1 | 5.691 | 0.029 |
Glycine cleavage system H protein, mitochondrial | GCSH | 5.495 | 0.020 |
Protein arginine N-methyltransferase 5 | PRMT5 | 5.495 | 0.020 |
Superoxide dismutase (Cu-Zn) | SOD1 | 5.443 | 0.003 |
Seizure 6-like protein 2 | SEZ6L2 | 4.820 | 0.002 |
Tetraspanin-10 | TSPAN10 | 4.669 | 0.040 |
Sortilin | SORT1 | 4.492 | 0.041 |
Cysteine-rich motor neuron 1 protein | CRIM1 | 4.437 | 0.009 |
Sodium-coupled neutral amino acid transporter 2 | SLC38A2 | 4.106 | 0.021 |
6-phosphofructokinase, muscle type | PFKM | 3.903 | 0.015 |
Laminin subunit α-5 | LAMA5 | 3.788 | 0.011 |
Tubulin--tyrosine ligase-like protein 12 | TTLL12 | 3.621 | 0.035 |
Melanocyte protein PMEL | PMEL | 3.123 | 0.021 |
Paxillin | PXN | 3.097 | 0.029 |
3-hydroxyisobutyrate dehydrogenase, mitochondrial | HIBADH | 3.056 | 0.030 |
Plexin-B2 | PLXNB2 | 3.049 | 0.011 |
40S ribosomal protein S28 | RPS28 | 2.956 | 0.034 |
CD44 antigen | CD44 | 2.956 | 0.034 |
Cullin-associated NEDD8-dissociated protein 1 | CAND1 | 2.951 | 0.049 |
Transferrin receptor protein 1 | TFRC | 2.847 | 0.029 |
Amyloid β A4 protein | APP | 2.838 | 0.001 |
Calpain-1 catalytic subunit | CAPN1 | 2.751 | 0.026 |
60S ribosomal protein L18a | RPL18A | 2.704 | 0.007 |
Proteasome subunit β type-4 | PSMB4 | 2.692 | 0.026 |
7-dehydrocholesterol reductase | DHCR7 | 2.600 | 0.048 |
60S ribosomal protein L13 | RPL13 | 2.551 | 0.009 |
Small nuclear ribonucleoprotein G | SNRPG | 2.551 | 0.009 |
NADH dehydrogenase (ubiquinone) iron-sulfur protein 2, mitochondrial | NDUFS2 | 2.546 | 0.018 |
Sequestosome-1 | SQSTM1 | 2.487 | 0.001 |
Heterogeneous nuclear ribonucleoprotein A1 | HNRNPA1 | 2.416 | 0.023 |
HLA class I histocompatibility antigen, B-8 α chain | HLA-B | 2.365 | 0.031 |
Laminin subunit γ-1 | LAMC1 | 2.334 | 0.006 |
Eukaryotic translation initiation factor 4H | EIF4H | 2.252 | 0.019 |
Rab GDP dissociation inhibitor β | GDI2 | 2.245 | 0.028 |
Actin-related protein 2 | ACTR2 | 2.228 | 0.022 |
Amyloid-like protein 2 | APLP2 | 2.203 | 0.042 |
GTP-binding nuclear protein Ran | RAN | 2.202 | 0.009 |
Syntenin-1 | SDCBP | 2.173 | 0.006 |
Integrin α-3 | ITGA3 | 2.142 | 0.027 |
Tropomodulin-3 | TMOD3 | 2.131 | 0.016 |
HLA class I histocompatibility antigen, Cw-12 α chain | HLA-C | 2.065 | 0.012 |
Fatty acid synthase | FASN | 2.050 | 0.025 |
HLA class I histocompatibility antigen, A-30 α chain | HLA-A | 2.014 | 0.006 |
Guanine nucleotide-binding protein G(s) subunit α isoforms XLas | GNAS | 1.995 | 0.010 |
Catechol O-methyltransferase | COMT | 1.899 | 0.045 |
Connective tissue growth factor | CTGF | 1.881 | 0.049 |
Ubiquitin carboxyl-terminal hydrolase isozyme L1 | UCHL1 | 1.861 | 0.036 |
Serpin H1 | SERPINH1 | 1.851 | 0.003 |
Thioredoxin reductase 1, cytoplasmic | TXNRD1 | 1.807 | 0.049 |
Pyruvate dehydrogenase E1 component subunit β, mitochondrial | PDHB | 1.784 | 0.004 |
WD repeat-containing protein 1 | WDR1 | 1.776 | 0.009 |
Laminin subunit β-1 | LAMB1 | 1.768 | 0.049 |
Importin subunit β-1 | KPNB1 | 1.763 | 0.048 |
Ribonuclease inhibitor | RNH1 | 1.744 | 0.023 |
T-complex protein 1 subunit eta | CCT7 | 1.680 | 0.011 |
Fructose-bisphosphate aldolase A | ALDOA | 1.643 | 0.023 |
γ-enolase | ENO2 | 1.598 | 0.017 |
Cation-independent mannose-6-phosphate receptor | IGF2R | 1.575 | 0.009 |
S-formylglutathione hydrolase | ESD | 1.573 | 0.025 |
14-3-3 protein β/α | YWHAB | 1.515 | 0.037 |
Heat shock protein HSP 90-α | HSP90AA1 | 1.460 | 0.025 |
Dihydropyrimidinase-related protein 2 | DPYSL2 | 1.452 | 0.033 |
Myoferlin | MYOF | 1.349 | 0.044 |
Coronin-1C | CORO1C | 1.235 | 0.030 |
Protein Name | Gene Symbol | FC | p-Value |
---|---|---|---|
Ras-related protein Rab-5A | RAB5A | 0.000 | 0.047 |
Collagen α-2(I) chain | COL1A2 | 0.000 | 0.041 |
Myosin phosphatase Rho-interacting protein | MPRIP | 0.000 | 0.024 |
Collagen α-1(XII) chain | COL12A1 | 0.000 | 0.021 |
Fibulin-1 | FBLN1 | 0.000 | 0.021 |
Lamina-associated polypeptide 2, isoforms β/γ | TMPO | 0.000 | 0.021 |
Zinc finger protein ubi-d4 | DPF2 | 0.000 | 0.021 |
Lysyl oxidase homolog 1 | LOXL1 | 0.000 | 0.019 |
Armadillo repeat-containing protein 10 | ARMC10 | 0.000 | 0.018 |
Heterogeneous nuclear ribonucleoprotein D-like | HNRNPDL | 0.000 | 0.018 |
Tetraspanin-6 | TSPAN6 | 0.000 | 0.018 |
Collagen α-1(I) chain | COL1A1 | 0.000 | 0.012 |
Cysteine-rich with EGF-like domain protein 1 | CRELD1 | 0.000 | 0.010 |
Fragile X mental retardation syndrome-related protein 2 | FXR2 | 0.000 | 0.010 |
Prolyl endopeptidase | PREP | 0.000 | 0.010 |
Ras-related protein Rab-13 | RAB13 | 0.000 | 0.010 |
RNA-binding protein 42 | RBM42 | 0.000 | 0.010 |
Keratin, type I cytoskeletal 9 | KRT9 | 0.000 | 0.008 |
Ephrin type-B receptor 2 | EPHB2 | 0.000 | 0.007 |
Single-stranded DNA-binding protein, mitochondrial | SSBP1 | 0.000 | 0.007 |
Transformer-2 protein homolog α | TRA2A | 0.000 | 0.007 |
Collagen α-1(V) chain | COL5A1 | 0.000 | 0.006 |
Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial | HADH | 0.000 | 0.006 |
Prolyl 4-hydroxylase subunit α-1 | P4HA1 | 0.000 | 0.004 |
Keratin, type I cytoskeletal 17 | KRT17 | 0.049 | 0.001 |
Keratin, type II cytoskeletal 1 | KRT1 | 0.063 | 0.013 |
Keratin, type I cytoskeletal 10 | KRT10 | 0.075 | 0.038 |
Septin-11 | SEPT11 | 0.114 | 0.002 |
AP-2 complex subunit β | AP2B1 | 0.121 | 0.043 |
Prolyl 3-hydroxylase 3 | LEPREL2 | 0.136 | 0.021 |
Putative tropomyosin α-3 chain-like protein | TPM3L | 0.146 | 0.018 |
Serine/arginine-rich splicing factor 1 | SRSF1 | 0.173 | 0.026 |
Septin-7 | SEPT7 | 0.174 | 0.038 |
S-phase kinase-associated protein 1 | SKP1 | 0.207 | 0.047 |
Myristoylated alanine-rich C-kinase substrate | MARCKS | 0.217 | 0.020 |
Dynactin subunit 1 | DCTN1 | 0.228 | 0.039 |
Epiplakin | EPPK1 | 0.250 | 0.015 |
Versican core protein | VCAN | 0.259 | 0.016 |
EGF-containing fibulin-like extracellular matrix protein 1 | EFEMP1 | 0.271 | 0.016 |
Y-box-binding protein 3 | YBX3 | 0.294 | 0.026 |
Basement membrane-specific heparan sulfate proteoglycan core protein | HSPG2 | 0.300 | 0.004 |
Myosin regulatory light polypeptide 9 | MYL9 | 0.331 | 0.032 |
Collagen α-1(XVIII) chain | COL18A1 | 0.338 | 0.004 |
Fibronectin | FN1 | 0.365 | 0.007 |
U1 small nuclear ribonucleoprotein 70 kDa | SNRNP70 | 0.374 | 0.031 |
Fibrillin-2 | FBN2 | 0.390 | 0.001 |
X-ray repair cross-complementing protein 6 | XRCC6 | 0.397 | 0.021 |
Fibulin-2 | FBLN2 | 0.398 | 0.005 |
Fibrillin-1 | FBN1 | 0.419 | 0.001 |
Histone H4 | HIST1H4A | 0.442 | 0.007 |
β-galactosidase | GLB1 | 0.452 | 0.026 |
Nodal modulator 3 | NOMO3 | 0.456 | 0.021 |
Drebrin | DBN1 | 0.472 | 0.037 |
Histone H3.1 | HIST1H3A | 0.481 | 0.015 |
Calmodulin | CALM1 | 0.487 | 0.022 |
General transcription factor II-I | GTF2I | 0.551 | 0.028 |
Myosin regulatory light chain 12B | MYL12B | 0.563 | 0.001 |
Spectrin α chain, nonerythrocytic 1 | SPTAN1 | 0.613 | 0.024 |
Golgi-associated plant pathogenesis-related protein 1 | GLIPR2 | 0.638 | 0.013 |
N-acetylglucosamine-6-sulfatase | GNS | 0.667 | 0.021 |
Calnexin | CANX | 0.675 | 0.028 |
Protein disulfide-isomerase A3 | PDIA3 | 0.681 | 0.006 |
Voltage-dependent anion-selective channel protein 3 | VDAC3 | 0.685 | 0.007 |
Actin, cytoplasmic 1 | ACTB | 0.690 | 0.013 |
Actin, cytoplasmic 2 | ACTG1 | 0.690 | 0.012 |
Prelamin-A/C | LMNA | 0.698 | 0.013 |
Calreticulin | CALR | 0.740 | 0.020 |
Tubulin β-4A chain | TUBB4A | 0.836 | 0.040 |
Tubulin β-4B chain | TUBB4B | 0.892 | 0.031 |
Protein Name | MS/MS | Immunofluorescence | Immunoblotting | |||
---|---|---|---|---|---|---|
FC | p-Value | FC | p-Value | FC | p-Value | |
CYR61 | 7.3 | 0.02 | 1.10 | 0.17 | 1.05 | 0.90 |
Laminin subunit β-2 | 10.5 | 0.001 | 1.91 | 0.007 | 1.11 | 0.43 |
Superoxide dismutase | 5.4 | 0.003 | 1.22 | 0.25 | 1.36 | 0.23 |
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Khan, A.Z.; Jackson, C.J.; Utheim, T.P.; Reppe, S.; Sapkota, D.; Olstad, O.K.; Thiede, B.; Eidet, J.R. Sericin-Induced Melanogenesis in Cultured Retinal Pigment Epithelial Cells Is Associated with Elevated Levels of Hydrogen Peroxide and Inflammatory Proteins. Molecules 2020, 25, 4395. https://doi.org/10.3390/molecules25194395
Khan AZ, Jackson CJ, Utheim TP, Reppe S, Sapkota D, Olstad OK, Thiede B, Eidet JR. Sericin-Induced Melanogenesis in Cultured Retinal Pigment Epithelial Cells Is Associated with Elevated Levels of Hydrogen Peroxide and Inflammatory Proteins. Molecules. 2020; 25(19):4395. https://doi.org/10.3390/molecules25194395
Chicago/Turabian StyleKhan, Ayyad Zartasht, Catherine Joan Jackson, Tor Paaske Utheim, Sjur Reppe, Dipak Sapkota, Ole Kristoffer Olstad, Bernd Thiede, and Jon Roger Eidet. 2020. "Sericin-Induced Melanogenesis in Cultured Retinal Pigment Epithelial Cells Is Associated with Elevated Levels of Hydrogen Peroxide and Inflammatory Proteins" Molecules 25, no. 19: 4395. https://doi.org/10.3390/molecules25194395