PMID- 31426598
OWN - NLM
STAT- MEDLINE
DCOM- 20200116
LR  - 20231213
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 24
IP  - 16
DP  - 2019 Aug 18
TI  - Development of Organelle Replacement Therapy Using a Stearyl-Polyhistidine 
      Peptide against Lysosomal Storage Disease Cells.
LID - 10.3390/molecules24162995 [doi]
LID - 2995
AB  - We previously reported on a polyhistidine peptide, His16 peptide, as a new 
      cell-penetrating peptide. This peptide is anticipated to be a new carrier for 
      drug delivery systems (DDSs) for targeting intracellular lysosomes because it can 
      transport macromolecules (e.g., liposomes) into these organelles. In the present 
      study, we examined the application of His16 peptide as a DDS carrier against 
      lysosomal storage disease (LSD) cells. LSDs are metabolic disorders caused by 
      loss of specific lysosomal enzymes. For the treatment of LSD cells, we devised a 
      system designated organelle replacement therapy (ORT). ORT is a strategy for 
      transporting exogenous lysosomes containing all kinds of lysosomal enzymes from 
      normal cells into endogenous lysosomes in LSD cells using His16 peptide. To 
      develop the ORT system, we prepared His16 peptide-modified healthy lysosomes 
      (His16-Lyso) by insertion of a stearyl-His16 peptide into a hydrophobic region in 
      the lysosomal membrane. His16-Lyso showed cellular uptake and localization to 
      endogenous lysosomes in LSD cells. His16-Lyso also restored the proliferation of 
      LSD cells, which otherwise showed slower proliferation than normal cells. These 
      results suggested that His16-Lyso replenished deficient lysosomal enzymes in LSD 
      cells. The results further suggest that His16-Lyso are promising candidates as a 
      treatment tool for LSD cells and to establish a foundation for ORT.
FAU - Hayashi, Taiki
AU  - Hayashi T
AD  - Department of Agricultural Science, Graduate School of Sustainability Science, 
      Tottori University, Tottori 680-8553, Japan.
FAU - Okamoto, Riku
AU  - Okamoto R
AD  - Department of Bioresources Science, Faculty of Agriculture, Tottori University, 
      Tottori 680-8553, Japan.
FAU - Kawano, Tsuyoshi
AU  - Kawano T
AD  - Department of Agricultural Science, Graduate School of Sustainability Science, 
      Tottori University, Tottori 680-8553, Japan.
FAU - Iwasaki, Takashi
AU  - Iwasaki T
AD  - Department of Agricultural Science, Graduate School of Sustainability Science, 
      Tottori University, Tottori 680-8553, Japan. itaka@tottori-u.ac.jp.
LA  - eng
GR  - 15K18689/Japan Society for the Promotion of Science/
PT  - Journal Article
DEP - 20190818
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Cell-Penetrating Peptides)
RN  - 0 (Drug Carriers)
RN  - 0 (LAMP1 protein, human)
RN  - 0 (Luminescent Proteins)
RN  - 0 (Lysosomal Membrane Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 26062-48-6 (polyhistidine)
RN  - 4QD397987E (Histidine)
SB  - IM
MH  - Biological Transport
MH  - Cell Engineering/*methods
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Cell-Penetrating Peptides/chemical synthesis/*metabolism
MH  - *Drug Carriers
MH  - Fabry Disease/pathology/therapy
MH  - Fibroblasts/metabolism/pathology
MH  - Gene Expression
MH  - Histidine/chemical synthesis/*metabolism
MH  - Humans
MH  - Hydrophobic and Hydrophilic Interactions
MH  - Luminescent Proteins/genetics/metabolism
MH  - Lysosomal Membrane Proteins/genetics/metabolism
MH  - Lysosomes/chemistry/metabolism/*transplantation
MH  - Models, Biological
MH  - Molecular Targeted Therapy/methods
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Red Fluorescent Protein
PMC - PMC6720886
OTO - NOTNLM
OT  - Fabry disease
OT  - cell-penetrating peptide
OT  - drug delivery system
OT  - histidine
OT  - lysosome
OT  - lysosome storage disease
COIS- The authors declare no conflict of interest.
EDAT- 2019/08/21 06:00
MHDA- 2020/01/17 06:00
PMCR- 2019/08/18
CRDT- 2019/08/21 06:00
PHST- 2019/07/11 00:00 [received]
PHST- 2019/08/16 00:00 [revised]
PHST- 2019/08/17 00:00 [accepted]
PHST- 2019/08/21 06:00 [entrez]
PHST- 2019/08/21 06:00 [pubmed]
PHST- 2020/01/17 06:00 [medline]
PHST- 2019/08/18 00:00 [pmc-release]
AID - molecules24162995 [pii]
AID - molecules-24-02995 [pii]
AID - 10.3390/molecules24162995 [doi]
PST - epublish
SO  - Molecules. 2019 Aug 18;24(16):2995. doi: 10.3390/molecules24162995.