#METABOLOMICS WORKBENCH Giovanni_DAngelo_20210129_041443 DATATRACK_ID:2433 STUDY_ID:ST001672 ANALYSIS_ID:AN002730 VERSION 1 CREATED_ON 03-03-2022 #PROJECT PR:PROJECT_TITLE Targeted Sphingolipid analysis of human Fibroblasts silenced for or PR:PROJECT_TITLE overexpressing GOLPH3 PR:PROJECT_SUMMARY A group of sequentially-acting enzymes operating at the branchpoint among PR:PROJECT_SUMMARY sphingolipid synthetic pathways binds the Golgi-localised oncoprotein GOLPH3. PR:PROJECT_SUMMARY GOLPH3 sorts these enzymes into vesicles for intra-Golgi retro-transport, acting PR:PROJECT_SUMMARY as a component of the cisternae inter-conversion mechanisms. Through these PR:PROJECT_SUMMARY effects, GOLPH3 controls the sub-Golgi localisation, and the lysosomal PR:PROJECT_SUMMARY degradation rate of specific enzymes. Here we evaluated the impact of PR:PROJECT_SUMMARY overexpressing or silencing GOLPH3 on the sphingolipid composition of dermal PR:PROJECT_SUMMARY human fibroblasts by targeted lipid analysis. PR:INSTITUTE École polytechnique fédérale de Lausanne (EPFL) PR:DEPARTMENT IBI PR:LABORATORY UPDANGELO PR:LAST_NAME D'Angelo PR:FIRST_NAME Giovanni PR:ADDRESS Station 15 CH1015 Lausanne Switzerland PR:EMAIL giovanni.dangelo@epfl.ch PR:PHONE +41 216934276 PR:DOI http://dx.doi.org/10.21228/M8R97G #STUDY ST:STUDY_TITLE Targeted Sphingolipid analysis of human Fibroblasts silenced for or ST:STUDY_TITLE overexpressing GOLPH3 (part-I) ST:STUDY_SUMMARY A group of sequentially-acting enzymes operating at the branchpoint among ST:STUDY_SUMMARY sphingolipid synthetic pathways binds the Golgi-localised oncoprotein GOLPH3. ST:STUDY_SUMMARY GOLPH3 sorts these enzymes into vesicles for intra-Golgi retro-transport, acting ST:STUDY_SUMMARY as a component of the cisternae inter-conversion mechanisms. Through these ST:STUDY_SUMMARY effects, GOLPH3 controls the sub-Golgi localisation, and the lysosomal ST:STUDY_SUMMARY degradation rate of specific enzymes. Here we evaluated the impact of ST:STUDY_SUMMARY overexpressing or silencing GOLPH3 on the sphingolipid composition of dermal ST:STUDY_SUMMARY human fibroblasts by targeted lipid analysis. ST:INSTITUTE École polytechnique fédérale de Lausanne (EPFL) ST:DEPARTMENT IBI ST:LABORATORY UPDANGELO ST:LAST_NAME D'Angelo ST:FIRST_NAME Giovanni ST:ADDRESS Station 15 CH1015 Lausanne Switzerland ST:EMAIL giovanni.dangelo@epfl.ch ST:PHONE +41 216934276 ST:SUBMIT_DATE 2021-01-29 #SUBJECT SU:SUBJECT_TYPE Cultured cells SU:SUBJECT_SPECIES Homo sapiens SU:TAXONOMY_ID 9606 #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Additional sample data SUBJECT_SAMPLE_FACTORS - GOLPH3_OE_1 Treatment:GOLPH3 overexpression RAW_FILE_NAME=GOLPH3_OE_1.raw SUBJECT_SAMPLE_FACTORS - GOLPH3_OE_2 Treatment:GOLPH3 overexpression RAW_FILE_NAME=GOLPH3_OE_2.raw SUBJECT_SAMPLE_FACTORS - GOLPH3_OE_3 Treatment:GOLPH3 overexpression RAW_FILE_NAME=GOLPH3_OE_3.raw SUBJECT_SAMPLE_FACTORS - GOLPH3_KD_1 Treatment:GOLPH3 silencing RAW_FILE_NAME=GOLPH3_KD_1.raw SUBJECT_SAMPLE_FACTORS - GOLPH3_KD_2 Treatment:GOLPH3 silencing RAW_FILE_NAME=GOLPH3_KD_2.raw SUBJECT_SAMPLE_FACTORS - GOLPH3_KD_3 Treatment:GOLPH3 silencing RAW_FILE_NAME=GOLPH3_KD_3.raw SUBJECT_SAMPLE_FACTORS - CTRL_1 Treatment:no treatment RAW_FILE_NAME=CTRL_1.raw SUBJECT_SAMPLE_FACTORS - CTRL_2 Treatment:no treatment RAW_FILE_NAME=CTRL_2.raw SUBJECT_SAMPLE_FACTORS - CTRL_3 Treatment:no treatment RAW_FILE_NAME=CTRL_3.raw #COLLECTION CO:COLLECTION_SUMMARY Cells were washed with ice cold PBS and draped CO:SAMPLE_TYPE Fibroblasts #TREATMENT TR:TREATMENT_SUMMARY Cells were either infected adenoviruses encoding GOLPH3 or treated with siRNAs TR:TREATMENT_SUMMARY targeting GOLPH3 expression #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Samples were fortified with an Internal standard Mix and lipids were extracted SP:SAMPLEPREP_SUMMARY twice with an extraction mix consisting of 85:15 Ethyl acetate 70% Isopropanol. SP:SAMPLEPREP_SUMMARY All lipids that were used in the Internal standard mix and in the Calibration SP:SAMPLEPREP_SUMMARY mixes were purchased from Avanti Polar Lipids Inc. After evaporating the cell SP:SAMPLEPREP_SUMMARY extract to dryness, the samples were reconstituted in the mobile phase. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY Samples were analyzed with a Quantum Ultra triple quadrupole mass spectrometer CH:CHROMATOGRAPHY_SUMMARY connected to an Accela HPLC and Accela autosampler using a solvent gradient. CH:CHROMATOGRAPHY_SUMMARY Ceramides identity was achieved through MRM analysis with soft fragmentation. CH:CHROMATOGRAPHY_SUMMARY Quantitative analysis is based on calibration curves generated for each CH:CHROMATOGRAPHY_SUMMARY ceramide. CH:INSTRUMENT_NAME Thermo Accela 1250 CH:COLUMN_NAME Thermo Accucore C18 (100 2.1mm, 2.6um) CH:CHROMATOGRAPHY_TYPE Reversed phase #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Quantum Ultra MS:INSTRUMENT_TYPE Triple quadrupole MS:MS_TYPE ESI MS:MS_COMMENTS Samples were analyzed with a Quantum Ultra triple quadrupole mass spectrometer MS:MS_COMMENTS connected to an Accela HPLC and Accela autosampler using a solvent gradient. MS:MS_COMMENTS Ceramides identity was achieved through MRM analysis with soft fragmentation. MS:MS_COMMENTS Quantitative analysis is based on calibration curves generated for each MS:MS_COMMENTS ceramide. J. Bielawski et al. / Methods 39 (2006) 82–91 MS:ION_MODE POSITIVE #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS pmol MS_METABOLITE_DATA_START Samples GOLPH3_OE_1 GOLPH3_OE_2 GOLPH3_OE_3 GOLPH3_KD_1 GOLPH3_KD_2 GOLPH3_KD_3 CTRL_1 CTRL_2 CTRL_3 Factors Treatment:GOLPH3 overexpression Treatment:GOLPH3 overexpression Treatment:GOLPH3 overexpression Treatment:GOLPH3 silencing Treatment:GOLPH3 silencing Treatment:GOLPH3 silencing Treatment:no treatment Treatment:no treatment Treatment:no treatment C14_cer 4.4310 4.9560 3.8750 10.3440 9.9170 7.9090 9.4780 7.2560 5.9580 C14HexosylCer 1.0160 1.0110 1.0160 1.1430 1.3490 1.1270 1.2660 1.4170 1.3670 C14Lact-Cer C14-SM 71.7190 83.6620 64.7760 83.5500 89.0080 69.2890 118.1170 74.0240 67.6300 C16_cer 64.4760 72.6400 60.5150 180.7270 164.0680 134.8980 137.8050 112.3070 97.0640 C16HexosylCer 37.0560 39.4970 32.2980 57.3640 67.0940 46.5620 45.2060 61.3050 51.1870 C16Lact-Cer 26.9720 30.5260 26.1470 17.6030 19.9750 14.7640 28.3920 21.2350 19.1640 C16-SM 1678.8530 1864.6400 1532.4070 2002.1030 2118.5160 1656.6080 2692.3540 1543.9480 1445.6090 C18_1_cer 1.5210 1.6770 1.4370 3.0860 3.0170 2.4790 3.6530 2.8670 2.3390 C18_1HexosylCer 1.9130 1.8410 1.9230 2.1860 2.2760 2.0220 1.9910 1.9760 1.8830 C18_1Lact-Cer C18_1-SM 13.8440 13.8690 12.6290 14.4420 14.9560 13.0330 16.2120 16.9890 15.2390 C18_cer 7.2380 7.9580 7.0460 16.9600 15.8220 13.2960 17.7870 14.9720 12.9000 C18HexosylCer 3.1340 3.1360 2.6380 4.0740 4.2490 3.5170 3.0450 3.2200 2.9390 C18Lact-Cer 1.7720 1.9400 1.8490 1.7040 1.1660 1.2480 2.7540 1.3030 1.0450 C18-SM 53.4620 56.6890 50.2280 56.2920 54.4170 49.7470 58.1290 49.5250 46.1770 C20_1_cer 0.6130 0.6900 0.5920 1.1720 1.2750 0.9890 1.4110 1.1290 1.0540 C20_1HexosylCer 1.1930 1.1690 1.1590 1.3330 1.2180 1.2340 1.1860 1.2080 1.1670 C20_1Lact-Cer C20_1-SM 0.9220 0.6390 1.1230 1.3750 1.3820 1.5820 1.6030 0.8560 0.9580 C20_cer 2.6190 3.2090 2.6510 6.3300 5.7660 4.6020 7.2870 5.4150 4.8920 C20HexosylCer 1.0790 1.1770 1.0730 1.8260 2.0720 1.8530 1.1170 1.1520 1.0220 C20Lact-Cer 0.0780 C20-SM 0.0190 0.4570 C22_1_cer 5.9090 6.4380 5.3900 13.1980 12.8230 9.9100 14.8830 10.4820 9.7910 C22_1HexosylCer 2.2120 2.0980 2.0540 3.0120 3.3390 2.7880 2.3800 2.3160 2.3130 C22_1Lact-Cer 2.5120 2.3220 2.4040 2.3770 2.3870 2.7350 2.4300 2.3660 2.3320 C22_1-SM 56.8050 57.6410 53.4550 66.2790 67.5150 63.2760 71.6030 56.7040 54.6060 C22_cer 24.1280 27.7710 22.2760 55.3340 52.5650 39.1570 52.6490 35.8310 29.2280 C22HexosylCer 28.8450 31.4190 27.5880 62.3120 69.6760 52.0950 36.2100 32.6930 26.6760 C22Lact-Cer 15.3550 15.5060 15.7010 14.7750 15.4480 14.1230 14.6640 10.9620 9.3930 C22-SM 121.7610 127.9640 115.7780 162.8480 164.5950 155.2660 141.6070 113.4730 109.2640 C24_1_cer 48.4450 54.0400 44.1550 92.5140 88.5990 72.1990 87.5460 58.1060 53.4280 C24_1HexosylCer 46.8510 52.4380 43.9680 69.9880 82.5280 60.7520 51.7390 59.8930 48.1400 C24_1Lact-Cer 27.7180 31.2750 28.8860 23.5570 25.6330 21.0600 25.0900 20.5320 19.9680 C24_1-SM 469.0460 502.5510 457.1470 469.1120 527.5500 492.0790 503.4530 457.7070 449.1740 C24_cer 54.0040 62.1790 50.3500 84.2340 81.1030 63.3790 78.0290 38.9240 37.5670 C24HexosylCer 184.4370 186.9950 162.5500 303.9520 346.5530 263.4370 201.1330 177.1570 141.8690 C24Lact-Cer 67.0260 71.9230 63.6910 46.5980 51.6840 42.0480 53.8110 39.3110 33.4020 C24-SM 243.4400 263.7080 234.2220 304.6830 315.5030 293.8120 266.8470 251.2550 227.0420 C26_1_cer 3.3280 3.7210 3.1070 4.7360 5.1590 3.8990 4.8460 2.7230 2.6490 C26_1HexosylCer 9.4800 10.0550 8.6560 16.2270 18.6920 15.3400 10.9730 12.5400 10.8770 C26_1Lact-Cer 5.2910 5.4900 5.7320 4.9600 5.3040 4.5700 4.9030 4.5110 3.6600 C26_1-SM 13.6220 16.4840 13.3870 20.9100 23.5700 23.9730 18.4310 17.7830 15.8190 C26_cer 2.4540 2.5220 2.2000 2.5270 2.7690 2.2870 2.7110 1.5620 1.8110 C26HexosylCer 4.3910 5.0970 4.8240 6.9350 7.8200 6.3900 5.2010 3.7710 3.8670 C26Lact-Cer 2.2240 2.5880 2.2510 1.9820 2.3350 2.0430 2.0720 2.0090 1.8020 C26-SM 4.6180 4.3750 3.6500 6.1720 6.1450 5.4830 4.7180 4.3920 3.7730 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name pubchem_id inchi_key kegg_id other_id other_id_type ri ri_type moverz_quant C14_cer 15.053 C14HexosylCer 15.979 C14Lact-Cer 15.552 C14-SM 17.662 C16_cer 16.57993424 C16HexosylCer 17.160 C16Lact-Cer 16.742 C16-SM 18.481 C18_1_cer 17.0608333 C18_1HexosylCer 17.550 C18_1Lact-Cer 16.744 C18_1-SM 19.081 C18_cer 17.93720568 C18HexosylCer 18.167 C18Lact-Cer 17.804 C18-SM 19.711 C20_1_cer 18.62231951 C20_1HexosylCer 18.170 C20_1Lact-Cer 17.808 C20_1-SM 19.964 C20_cer 19.3108956 C20HexosylCer 19.233 C20Lact-Cer 18.814 C20-SM 20.845 C22_1_cer 19.94082869 C22_1HexosylCer 19.455 C22_1Lact-Cer 19.037 C22_1-SM 20.658 C22_cer 20.77011827 C22HexosylCer 20.404 C22Lact-Cer 19.875 C22-SM 21.602 C24_1_cer 20.97331072 C24_1HexosylCer 20.576 C24_1Lact-Cer 20.046 C24_1-SM 21.729 C24_cer 22.3756384 C24HexosylCer 22.562 C24Lact-Cer 21.866 C24-SM 22.988 C26_1_cer 22.87423635 C26_1HexosylCer 21.748 C26_1Lact-Cer 21.109 C26_1-SM 23.083 C26_cer 24.53351824 C26HexosylCer 23.258 C26Lact-Cer 22.561 C26-SM 24.624 METABOLITES_END #END