Effects of Recombinant α1-Microglobulin on Early Proteomic Response in Risk Organs after Exposure to 177Lu-Octreotate
Abstract
:1. Introduction
2. Results
2.1. Absorbed Dose to Kidneys and Bone Marrow
2.2. Differentially Regulated Proteins, DRPs
2.3. Canonical Pathway Analysis
2.4. Upstream Regulators
2.5. Toxicity Functions
3. Discussion
4. Materials and Methods
4.1. Radiopharmaceutical
4.2. Recombinant α1-Microglobulin (A1M)
4.3. Animal Experiments
4.4. Radioactivity Measurements
4.5. Absorbed Dose Calculation
4.5.1. Bone Marrow
4.5.2. Kidneys
4.6. Proteomics
4.6.1. Sample Preparation and Digestion
4.6.2. Tryptic Digestion and Tandem Mass Tag (TMT) Labelling
4.6.3. LC-MS/MS Analysis
4.7. Proteomic Data Analysis
4.8. Analysis of Protein Regulation
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Mean Absorbed Dose (Gy) | ||||
---|---|---|---|---|
177Lu-Octreotate | 177Lu-Octreotate + A1M | |||
Time after Injection | 24 h | 7 d | 24 h | 7 d |
Bone marrow | 6.0 Gy | 21 Gy | 5.8 Gy | 19 Gy |
Kidney inner medulla | 28 Gy | 73 Gy | 27 Gy | 66 Gy |
Kidney cortex | 25 Gy | 64 Gy | 24 Gy | 58 Gy |
Total kidney | 25 Gy | 66 Gy | 25 Gy | 59 Gy |
24 h | 7 d | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
177Lu | 177Lu + A1M | A1M | 177Lu | 177Lu + A1M | A1M | |||||||
Kidney cortex | BCHE | −5.3 | BCHE | −4.2 | SAA2 | 4.7 | SNRK | −4.3 | POLK | 6.5 | KV2A7 * | 3.5 |
TGT.Z.P.1 | −3.8 | SAA2 | 3.5 | PLIN1 | −3.7 | GLE1 | −4.2 | CMA1 | 5.8 | SNRK | −3.1 | |
AQP4 | 3.1 | HP | 3.5 | BCHE | −3.1 | CACTIN | −3.7 | THRSP * | 5.1 | HP | 2.9 | |
SDSL | −3.1 | TGT.Z.P.1 | −3.3 | TGT.Z.P.1 | −2.9 | EPHX1 | 3.2 | SNRK | −3.8 | KV3A8 * | 2.9 | |
LSP1 | −3.0 | SDSL | −3.1 | C.Y.P2A4 | −2.8 | HDC | −3.1 | CACTIN | −3.2 | AQP4 | 2.8 | |
GLE1 | −2.6 | H2-AB1 | −3.0 | SAA1 | 2.7 | PLCD4 | 2.8 | EPHX1 | 3.1 | GCAB | 2.8 | |
H2-AB1 | −2.7 | KRT71 | 2.6 | SLC22A13 | −2.5 | POLK | 2.8 | PLCD4 | 2.9 | S100A9 * | 2.6 | |
CACTIN | −2.4 | C.Y.P2A4 | −2.5 | PNPLA2 | −2.6 | EDRF1 * | 2.9 | POLK | 2.6 | |||
SAA1 | 2.4 | AIF1 | −2.6 | PHLDA3 | 2.9 | HVM51 | 2.5 | |||||
POLK | 2.4 | MGMT | 2.5 | CELR3 | 2.8 | IGHG1 * | 2.5 | |||||
POLE3 | 2.5 | FABP4 | 2.7 | |||||||||
MGMT | 2.7 | |||||||||||
CA3 | 2.6 | |||||||||||
LTC4S | 2.5 | |||||||||||
Kidney medulla | KRT82 * | 6.3 | MCM3 | 6.5 | S100G | −3.1 | MITF | 6.9 | CCDC8 | −3.7 | KV2A7 | 3.0 |
RCSD1 | −4.0 | ECE1 | 6.4 | NCOR1 | −3.1 | BCHE | −4.4 | BCHE | −3.5 | BCHE | −2.9 | |
BCHE | −4.0 | BCHE | −3.4 | RCSD1 | −2.9 | CCDC8 | −4.4 | PHLDA3 | 3.4 | CCDC8 | −2.8 | |
KRT31 * | 3.9 | BMPR2 | −3.3 | PLIN1 | −2.9 | POLR1A | −3.4 | KAP | −3.2 | LCN2 * | 2.8 | |
BMPR2 | −3.9 | TTC7B | 3.3 | BMPR2 | −2.8 | PHLDA3 | 3.3 | POLR1A | −3.2 | CHIL3 * | 2.7 | |
NCOR1 | −3.3 | HP | 2.9 | BCHE | −2.7 | POLE3 | 3.2 | KRT16 | −2.9 | POLR1A | −2.7 | |
MCM3 | 3.0 | RCSD1 | −2.7 | YIPF1 | −2.7 | KAP | −2.9 | POLE3 | 2.8 | GCAB | 2.6 | |
KRT85 | 2.8 | SAA1 | 2.6 | SAA1 | 2.6 | KLHL8 | −2.8 | OXR1 C7 | −2.7 | TGFB1I1 | 2.5 | |
EHBP1 | −2.8 | A1BG | −2.5 | CDC26 | −2.4 | KRT16 | −2.6 | KLHL8 | −2.6 | KRT71 | −2.5 | |
KT33A | 2.7 | PHLDA3 | 2.3 | TMCO3 | −2.4 | MYH1 | −2.5 | MCM3 | 2.6 | ALDH1A3 | −2.4 | |
A1BG | −2.7 | PLIN1 | −2.3 | FAU | 2.4 | FAM107B | −2.2 | HVM54 | 2.3 | |||
FRM4B | −2.4 | NCOR1 | −2.3 | SAA2 | 2.3 | SMAGP | −2.2 | |||||
MAVS | −2.4 | MAVS | −2.1 | ARHGAP23 * | −2.3 | MYO9B | −2.2 | |||||
KAP | −2.3 | AT.Z.P.5PF | −2.2 | COL7A1 | −2.2 | |||||||
PHLDA3 | 2.3 | HSD17B2 | −2.2 | |||||||||
Bone marrow | SFN | −5.3 | SFN | −6.5 | SFN | −3.9 | BCHE | −6.7 | BCHE | −5.9 | MYH3 | 6.5 |
ABHD5 | −3.2 | TNNT2 | 4.7 | RSRC2 | 3.1 | NEK1 | 4.7 | MYH3 | 3.9 | ZNF787 | −5.4 | |
HELZ | −3.0 | ANKRD2 | 4.4 | ABHD5 | −3.1 | PIP5K1A | 4.1 | NEK1 | 3.5 | BCHE | −4.4 | |
GALNT7 | −2.6 | TNNI1 | 3.5 | ZNF280D | −2.8 | TNNT2 | −3.3 | PIP5K1A | 3.1 | MYLPF | 3.9 | |
RSRC2 | 2.4 | ABHD5 | −3.5 | HELZ | −2.7 | MYH7B | −3.2 | MYLPF | 3.1 | MYH4 | 3.9 | |
A1BG | −2.2 | MYL2 | 3.4 | SMAP | 2.5 | MYH7 | −2.8 | TNNT3 | 3.0 | ACTN3 | 3.8 | |
XRCC4 | −2.2 | MYL3 | 3.4 | SAA1 | 2.4 | MYL2 | −2.8 | CCDC167 | −2.9 | TNNT3 | 3.7 | |
MYH7 | 3.3 | KRT71 | 2.3 | KAT5 | 2.7 | ACTN3 | 2.9 | MFF | −3.6 | |||
CRYAB * | 3.2 | SATB2 | 2.3 | SERPINA1E | −2.6 | MYL1 | 2.8 | ZNF318 | 3.6 | |||
HSPB6 | 3.2 | TNNI2 | −2.3 | TNNC2 | 2.7 | AT.Z.P.2A1 | 3.5 | |||||
CPT1B | 3.2 | GALNT7 | −2.2 | ZNF787 | −2.7 | TMPO | −3.5 | |||||
HELZ | −2.9 | PLEK.H.A | 2.2 | AT.Z.P.2A1 | 2.7 | MYL1 | 3.4 | |||||
CKMT2 | 2.9 | RYR2 | −2.2 | DGCR6 | 2.7 | SARNP | −3.3 | |||||
RSRC2 | 2.9 | KAT5 | 2.6 | ACTA1 | 3.3 | |||||||
ACTN2 | 2.7 | TNNI2 | 2.6 | TNNI2 | 3.2 | |||||||
FABP3 | 2.7 | MYH1 | 2.6 | TNNC2 | 3.0 | |||||||
MYH4 | 2.5 | RSRC2 | −3.0 | |||||||||
ACTA1 | 2.4 | HABP4 | −3.0 | |||||||||
KRT6A | 2.4 | GCAB | 2.9 | |||||||||
CKS2 | −2.4 | CDCA2 | −2.8 | |||||||||
MAD2L1BP | −2.3 | IGHG1 * | 2.8 | |||||||||
AMPD1 | 2.2 | MYBPC2 | 2.8 | |||||||||
TMEM9 | −2.2 | NEB.L. | 2.6 | |||||||||
PTMS * | −2.5 | |||||||||||
TTN | 2.5 | |||||||||||
POLR2M | −2.5 | |||||||||||
SERPINA1E | −2.5 | |||||||||||
MYOM1 | 2.4 | |||||||||||
KRI1 | −2.4 | |||||||||||
MAD2L1BP | −2.4 | |||||||||||
AMPD1 | 2.4 | |||||||||||
CKS2 | −2.4 | |||||||||||
SNCA SYN | −2.4 |
Kidney Cortex | |||||
Time | Group | Ingenuity Canonical Pathways | p-Value | z-Score | Involved Proteins |
24 h | 177Lu + A1M | Estrogen receptor signaling * | 4.37 × 10−2 | −2.00 | ARG2, BAD, NCOR1, RAP2A |
7 d | 177Lu | Aryl hydrocarbon receptor signaling | 3.24 × 10−4 | −2.00 | BAX, MCM7, NCOA3, NCOR2, NQO1 |
Kidney Medulla | |||||
Time | Group | Ingenuity Canonical Pathways | p-Value | z-Score | Involved Proteins |
24 h | 177Lu + A1M | 3-phosphoinositide biosynthesis | 7.94 × 10−3 | −2.00 | PAWR, PIP5K1A, PPP1R1A, PPP1R1B |
Superpathway of inositol phosphate compounds | 1.45 × 10−2 | −2.00 | |||
A1M | 3-phosphoinositide biosynthesis | 1.35 × 10−2 | −2.00 | ||
Superpathway of inositol phosphate compounds | 2.45 × 10−2 | −2.00 | |||
Bone Marrow | |||||
Time | Group | Ingenuity Canonical Pathways | p-Value | z-Score | Involved Proteins |
24 h | 177Lu + A1M | Actin cytoskeleton signaling | 7.24 × 10−10 | 2.53 | ACTA1, ACTN2, CFL2, MYH1, MYH7, MYH8, MYL2, MYL3, MYL6B, MYLK2, MYLK3, MYLPF, TTN |
ILK signaling | 2.19 × 10−8 | 2.11 | ACTA1, ACTN2, CFL2, CREBBP, FLNC, MYH1, MYH7, MYH8, MYL2, MYL3, MYL6B | ||
Hepatic fibrosis signaling pathway | 8.13 × 10−5 | 2.53 | AXIN1, CREBBP, MYL2, MYL3, MYL6B, MYLK2, MYLK3, MYLPF, TRADD, TTN | ||
Regulation of actin-based motility by Rho | 2.34 × 10−4 | 2.24 | ACTA1, MYL2, MYL3, MYL6B, MYLPF | ||
PAK signaling | 3.02 × 10−4 | 2.00 | CFL2, MYL2, MYL3, YL6B, MYLPF | ||
Apelin cardiomyocyte signaling pathway | 3.47 × 10−4 | 2.24 | AT.Z.P.2A1, MYL2, MYL3, MYL6B, MYLPF | ||
Signaling by Rho family GT.Z.P.ases | 7.08 × 10−4 | 2.45 | ACTA1, CFL2, DES, MYL2, MYL3, MYL6B, MYLPF | ||
Cdc42 signaling | 2.34 × 10−3 | 2.24 | CFL2, MYL2, MYL3, MYL6B, MYLPF | ||
Cardiac hypertrophy signaling | 3.39 × 10−3 | 2.24 | CREBBP, HSPB1, MYL2, MYL3, MYL6B, MYLPF | ||
Gα12/13 signaling | 8.13 × 10−3 | 2.00 | MYL2, MYL3, MYL6B, MYLPF | ||
CXCR4 signaling | 1.82 × 10−2 | 2.00 | |||
A1M | Actin cytoskeleton signaling | 5.13 × 10−3 | −2.00 | Actn3, MYH3, MYH4, MYLK3, MYLPF | |
ILK signaling | 1.62 × 10−2 | −2.00 | Actn3, CREBBP, MYH3, MYH4 | ||
7d | 177Lu | ILK signaling | 3.55E × 10−5 | −2.45 | ACTN2, MYH7, MYH7B, MYL2, MYL3, MYL6B |
Phospholipase C signaling | 1.45 × 10−3 | −2.00 | ARHGEF18, GNB4, MYL2, MYL3, MYL6B | ||
177Lu + A1M | Calcium signaling | 5.01 × 10−12 | 2.24 | ACTA1, ACTC1, AT.Z.P.2A1, CACNA2D1, MYH1, MYH3, MYH4, MYH8, MYL1,RYR1, RYR2, TNNC2, TNNI2, TNNT2, TNNT3, Tpm1, Tpm2 | |
Actin cytoskeleton signaling | 4.90 × 10−6 | 3.16 | ACTA1, ACTC1, Actn3, MYH1, MYH3, MYH4, MYH8, MYL1, MYLPF, PIP5K1A, TTN | ||
ILK signaling | 6.03 × 10−5 | 2.33 | ACTA1, ACTC1, Actn3, FLNC, MYH1, MYH3, MYH4, MYH8, MYL1 | ||
Regulation of actin-based motility by Rho | 1.48 × 10−3 | 2.24 | ACTA1, ACTC1, MYL1, MYLPF, PIP5K1A | ||
Signaling by Rho family GT.Z.P.ases | 1.74 × 10−3 | 2.12 | ACTA1, ACTC1, ARHGEF18, DES, GFAP, MYL1, MYLPF, PIP5K1A | ||
Integrin signaling * | 4.37 × 10−2 | 2.23 | ACTA1, ACTC1, Actn3, CAPN7, TTN | ||
A1M | Calcium signaling | 1.62 × 10−9 | 2.00 | ACTA1, ACTC1, AT.Z.P.2A1, MYH1, MYH3, MYH4, MYH8, MYL1, MYL2, RYR1, RYR2, TNNC2, TNNI2, TNNT2, TNNT3, Tpm1, Tpm2 | |
Actin cytoskeleton signaling | 5.89 × 10−6 | 2.71 | ACTA1, ACTC1, Actn3, MYH1, MYH3, MYH4, MYH8, MYL1, MYL2, MYLK3, MYLPF, PIP5K1A, TTN |
Upstream Regulator | Tissue | Time | Group | Predicted State | Target Proteins in Dataset |
---|---|---|---|---|---|
Bvht | Bone marrow | 24 h | 177Lu + A1M | Activated | MYH7, MYL2, MYL3, MYOM1, SMYD1, TNNI1, TNNT2, TTN |
7 d | 177Lu | Inhibited | MYH7, MYL2, MYL3, TNNI1, TNNT2 | ||
DNMT3B | Bone marrow | 24 h | A1M | Activated | CASQ1, RYR2, TNNT2, TNNT3 |
7 d | 177Lu | Activated | MYH7, MYH7B, MYL2, MYL3, TNNI1, TNNT2 | ||
ETV6-RUNX1 | Cortex | 24 h | 177Lu | Activated | CORO1A, GBP2, PSMB9, PT.Z.P.RC |
Medulla | 24 h | 177Lu | Activated | CORO1A, C.Y.BB, GBP2, ITGB2, MGMT, PSMB9, PT.Z.P.RC, STMN1 | |
Ifnar | Cortex | 24 h | 177Lu | Inhibited | GBP2, IFIT1B, PSMB8, PSMB9, TAPBP, VCAM1 |
A1M | Inhibited | GBP2, PSMB8, PSMB9, TAP1, TAPBP | |||
IFNG | Cortex | 24 h | 177Lu + A1M | Inhibited | ACE, AIF1, ARG2, BBC3, C1QB, GBP2, HLA-DQB1, Iigp1, PSMB10, PSMB8, PSMB9, Tgtp1/Tgtp2 |
A1M | Inhibited | ACE, ARG2, GBP2, HLA-DQB1, Iigp1, PSMB8, PSMB9, SLC2A4, TAP1, TAPBP, Tgtp1/Tgtp2 | |||
Medulla | 24 h | 177Lu | Inhibited | AIF1, ALDH1A3, CD74, C.Y.BB, ECE1, GBP2, HLA-DQA1, HLA-DQB1, PARVG, PPP1R1B, PSMB9, SDC4, SMAGP, Tgtp1/Tgtp2 | |
IL10RA | Cortex | 24 h | 177Lu + A1M | Activated | ARG2, GBP2, Iigp1, LUM, MEP1A, PSMB8, PSMB9, Tgtp1/Tgtp2 |
7 d | 177Lu | Activated | CLIC6, IFI16, LTC4S, Tgtp1/Tgtp2 | ||
KDM5A | Bone marrow | 24 h | 177Lu + A1M | Inhibited | ACTN2, FXYD1, MYH7, MYH8, MYL6B, PGAM2, TNNC2, TNNT2, Tpm2, TRIM72 |
A1M | Activated | Actn3, FXYD1, MYH4, TNNC2, TNNI2, TNNT2 | |||
7 d | 177Lu | Activated | ACTN2, MYH7, MYL6B, TNNT2 | ||
177Lu + A1M | Inhibited | ACTC1, Actn3, MFN2, MYH4, MYH8, MYL1, PGAM2, RYR1, TNNC2, TNNI2, TNNT2, Tpm1, Tpm2, TRIM72 | |||
A1M | Inhibited | ACTC1, Actn3, MFN2, MYH4, MYH8, MYL1, PGAM2, RYR1, TNNC2, TNNI2, TNNT2, Tpm1, Tpm2, TRIM72 | |||
LHX1 | Cortex | 24 h | 177Lu + A1M | Inhibited | AADAT, Kap, MEP1A, MEP1B, SLC22A24 |
A1M | Inhibited | AADAT, Kap, MEP1A, MEP1B, SLC22A24 | |||
mir-21 | Cortex | 24 h | A1M | Activated | GBP2, Iigp1, TAP1, Tgtp1/Tgtp2 |
7 d | 177Lu + A1M | Activated | AIF1, COL1A1, COL3A1, IGHM, Tgtp1/Tgtp2 | ||
Medulla | 24 h | 177Lu | Activated | AIF1, BMPR2, GBP2, Tgtp1/Tgtp2 | |
MRTFA | Cortex | 7 d | A1M | Inhibited | CMA1, LCN2, LTF, Ngp, S100A9 |
Medulla | 7 d | A1M | Inhibited | CAMP, LCN2, Ngp, S100A9 | |
MRTFB | Cortex | 7 d | 177Lu + A1M | Inhibited | CMA1, LCN2, LTF, Ngp, S100A9 |
Medulla | 7 d | A1M | Inhibited | CAMP, LCN2, Ngp, S100A9 | |
MYOCD | Bone marrow | 24 h | 177Lu + A1M | Activated | ACTA1, ACTN2, DES, MYH7, MYL2, TNNI1, TNNT2, TTN |
7 d | 177Lu | Inhibited | ACTN2, MYH7, MYL2, TNNI1, TNNT2 | ||
MYOD1 | Bone marrow | 24 h | 177Lu + A1M | Activated | ACTA1, ANKRD2, AT.Z.P.2A1, CKM, DES, MYLPF, TNNC2, TNNT2 |
A1M | Inhibited | ANKRD2, MYH3, MYH4, MYLPF, TNNC2, TNNI2, TNNT2, TNNT3 | |||
7 d | 177Lu + A1M | Activated | ACTA1, AT.Z.P.2A1, DES, DM.D., ENO3, INPP5K, MYH3, MYH4, MYL1, MYLPF, TNNC2, TNNI2, TNNT2, TNNT3 | ||
A1M | Activated | ACTA1, AT.Z.P.2A1, DES, ENO3, MYH3, MYH4, MYL1, MYLPF, TNNC2, TNNI2, TNNT2, TNNT3 | |||
NOS2 | Cortex | 7 d | 177Lu + A1M | Inhibited | BAX, FABP4, FASN, KRT13, MB, Tgtp1/Tgtp2 |
Bone marrow | 24 h | 177Lu + A1M | Inhibited | ACTA1, COX6A2, COX7A1, MB, MYH7, MYL2, MYL3, TNNT2 | |
7d | A1M | Inhibited | ACTA1, ACTC1, CD3E, COX6A2, IGHG1, KRT13, MB, MYL2, TNNT2, TNNT3 | ||
NRAS | Cortex | 24 h | A1M | Activated | GBP2, Iigp1, PSMB8, TAP1, Tgtp1/Tgtp2 |
Medulla | 7 d | 177Lu | Inhibited | BAX, EPHX1, KCTD12, PHLDA3 | |
RB1 | Bone marrow | 24 h | 177Lu + A1M | Activated | ACTN2, CKM, COL5A1, FXYD1, MECR, MYH7, MYH8, MYL6B, PGAM2, TNNC2, TNNT2, Tpm2, TRIM72 |
7 d | 177Lu + A1M | Activated | ACTC1, Actn3, BAK1, BCL2L11, Esrra, Krt10, KRT5, LOXL2, MFN2, MYH4, MYH8, MYL1, PGAM2, RYR1, TNNC2, TNNI2, TNNT2, Tpm1, Tpm2, TRIM72, TUBG1, ZNF638 | ||
A1M | Activated | ACTC1, Actn3, BAK1, Krt10, LOXL2, MFN2, MYH4, MYH8, MYL1, PGAM2, RYR1, SAFB, TNNC2, TNNI2, TNNT2, Tpm1, Tpm2, TRIM72, ZNF638 | |||
SIRT1 | Cortex | 24 h | 177Lu | Activated | BBC3, CORO1A, HLA-DQB1, IFIT1B, Iigp1, PSMB9, Tgtp1/Tgtp2 |
177Lu + A1M | Activated | BBC3, CORO1A, HLA-DQB1, HMGCR, IFIT1B, Iigp1, PSMB9, Tgtp1/Tgtp2 | |||
A1M | Activated | HLA-DQB1, HMGCR, Iigp1, PSMB9, TAP1, Tgtp1/Tgtp2 | |||
SMTNL1 | Bone marrow | 24 h | 177Lu + A1M | Inhibited | ACTA1, FLNC, MYOM1, TNNC2, Tpm2 |
A1M | Activated | MYH4, TNNC2, TNNI2, TNNT3 | |||
7 d | 177Lu + A1M | Inhibited | ACTA1, FLNC, MYH4, MYL1, MYOM1, PYGM, TNNC2, TNNI2, TNNT3, Tpm1, Tpm2 | ||
A1M | Inhibited | ACTA1, FLNC, MYH4, MYL1, MYOM1, PYGM, TNNC2, TNNI2, TNNT3, Tpm1, Tpm2 | |||
SRF | Bone marrow | 24 h | 177Lu + A1M | Activated | ACTA1, CKM, DES, FHL1, LDB3, MYH1, MYH7, MYL3, MYOM1, Nebl, Tpm2, TTN |
7 d | 177Lu + A1M | Activated | ACTA1, ACTC1, BCL2L11, DES, DM.D., LDB3, MYH1, MYH4, MYL1, MYOM1, Nebl, Tpm1, Tpm2, TTN, TUBB4B | ||
A1M | Activated | ACTA1, ACTC1, AKAP12, DES, Igkv1-117, LDB3, MYH1, MYH4, MYL1, MYOM1, Nebl, Tpm1, Tpm2, TTN, TUBB4B | |||
STAT1 | Cortex | 24 h | 177Lu | Inhibited | CEACAM1, GBP2, IFIT1B, Iigp1, PSMB10, PSMB8, PSMB9, Tgtp1/Tgtp2 |
177Lu + A1M | Inhibited | BAD, Cyp2d9 (includes others), GBP2, IFIT1B, Iigp1, PSMB10, PSMB8, PSMB9, Tgtp1/Tgtp2 | |||
A1M | Inhibited | BAD, Cyp2d9 (includes others), GBP2, Iigp1, PSMB8, PSMB9, TAP1, Tgtp1/Tgtp2 | |||
Medulla | 24 h | 177Lu | Inhibited | ALDH1A3, BAD, CAND2, GBP2, HLA-DQA1, PSMB9, SMAGP, Tgtp1/Tgtp2 | |
TRIM24 | Cortex | 24 h | 177Lu | Activated | GBP2, IFIT1B, Iigp1, PSMB10, PSMB8, PSMB9, Tgtp1/Tgtp2 |
177Lu + A1M | Activated | GBP2, IFIT1B, Iigp1, PSMB10, PSMB8, PSMB9, Tgtp1/Tgtp2 | |||
A1M | Activated | GBP2, Iigp1, PSMB8, PSMB9, TAP1, Tgtp1/Tgtp2 | |||
Medulla | 24 h | 177Lu | Activated | GBP2, MGMT, PSMB9, Tgtp1/Tgtp2 |
Kidney Cortex | ||||||
Time | Treatment | Category | Function | p-Value | z-Score | Target Proteins in Dataset |
7 d | 177Lu + A1M | Renal inflammation, renal nephritis | Nephritis | 1.73 × 10−2 | −1.88 | FABP1, HLA-DQB1, DCN, IGHM, BAX, SIRT1, Uox |
Kidney Medulla | ||||||
Time | Treatment | Category | Function | p-Value | z-Score | Target Proteins in Dataset |
24 h | 177Lu | Glomerular injury | Glomerulosclerosis | 3.45 × 10−3 | −1.19 * | Kap, CDKN1B, REN, HMOX1, STMN1 |
24 h | 177Lu | Renal necrosis/ cell death | Cell death | 3.17 × 10−2 | −0.81 | MAVS, CDKN1B, SOD1, C.Y.BB, BAD, STMN1 |
7 d | 177Lu + A1M | Renal necrosis/ cell death ** | Cell viability | 8.66 × 10−4 | 1.45 | CAV1, BAX, ABCC10, MAPT |
7 d | A1M | Renal necrosis/ cell death ** | Cell death | 2.69 × 10−2 | 0.14 | PTGDS, TGFB1I1, SOD1, CALB1, LCN2 |
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Ytterbrink, C.; Shubbar, E.; Parris, T.Z.; Langen, B.; Druid, M.; Schüler, E.; Strand, S.-E.; Åkerström, B.; Gram, M.; Helou, K.; et al. Effects of Recombinant α1-Microglobulin on Early Proteomic Response in Risk Organs after Exposure to 177Lu-Octreotate. Int. J. Mol. Sci. 2024, 25, 7480. https://doi.org/10.3390/ijms25137480
Ytterbrink C, Shubbar E, Parris TZ, Langen B, Druid M, Schüler E, Strand S-E, Åkerström B, Gram M, Helou K, et al. Effects of Recombinant α1-Microglobulin on Early Proteomic Response in Risk Organs after Exposure to 177Lu-Octreotate. International Journal of Molecular Sciences. 2024; 25(13):7480. https://doi.org/10.3390/ijms25137480
Chicago/Turabian StyleYtterbrink, Charlotte, Emman Shubbar, Toshima Z. Parris, Britta Langen, Malin Druid, Emil Schüler, Sven-Erik Strand, Bo Åkerström, Magnus Gram, Khalil Helou, and et al. 2024. "Effects of Recombinant α1-Microglobulin on Early Proteomic Response in Risk Organs after Exposure to 177Lu-Octreotate" International Journal of Molecular Sciences 25, no. 13: 7480. https://doi.org/10.3390/ijms25137480