Abstract |
Erectile dysfunction (ED) is a common and debilitating condition with high impact on quality of life. An underlying cause of ED is apoptosis of penile smooth muscle, which occurs with cavernous nerve injury, in prostatectomy, diabetic and aging patients. We are developing peptide amphiphile (PA) nanofiber hydrogels as an in vivo delivery vehicle for Sonic hedgehog protein to the penis and cavernous nerve to prevent the apoptotic response. We examine two important aspects required for clinical application of the biomaterials: if SHH PA suppresses intrinsic ( caspase 9) and extrinsic ( caspase 8) apoptotic mechanisms, and if suppressing one apoptotic mechanism forces apoptosis to occur via a different mechanism. We show that SHH PA suppresses both caspase 9 and 8 apoptotic mechanisms, and suppressing caspase 9 did not shift signaling to caspase 8. SHH PA has significant clinical potential as a preventative ED therapy, by management of intrinsic and extrinsic apoptotic mechanisms.
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Authors | Sarah Martin, Daniel A Harrington, Samuel Ohlander, Samuel I Stupp, Kevin T McVary, Carol A Podlasek |
Journal | Nanomedicine : nanotechnology, biology, and medicine
(Nanomedicine)
Vol. 37
Pg. 102444
(10 2021)
ISSN: 1549-9642 [Electronic] United States |
PMID | 34314869
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Published by Elsevier Inc. |
Chemical References |
- Hedgehog Proteins
- Hydrogels
- Peptides
- SHH protein, human
- Caspase 8
- Caspase 9
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Topics |
- Animals
- Apoptosis
(drug effects)
- Caspase 8
(genetics)
- Caspase 9
(genetics)
- Cavernous Sinus
(drug effects, pathology)
- Disease Models, Animal
- Erectile Dysfunction
(drug therapy, genetics, pathology)
- Hedgehog Proteins
(chemistry, genetics, pharmacology)
- Humans
- Hydrogels
(chemistry, pharmacology)
- Male
- Nanofibers
(chemistry)
- Penis
(drug effects, pathology)
- Peptides
(chemistry, pharmacology)
- Prostatectomy
(adverse effects)
- Rats
- Rats, Sprague-Dawley
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