Heat Shock Protein 70 in Penile Neurovascular Regeneration Requires Cystathionine Gamma-Lyase
Purpose: Diabetes mellitus, one of the major causes of erectile dysfunction, leads to a poor response to phosphodiesterase-5 inhibitors. Heat shock protein 70 (Hsp70), a ubiquitous molecular chaperone, is known to play a role in cell survival and neuroprotection. Here, we aimed to assess whether a...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Korean Society for Sexual Medicine and Andrology
2022-10-01
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| Series: | The World Journal of Men's Health |
| Subjects: |
| _version_ | 1828149084767125504 |
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| author | Kalyan Ghatak Guo Nan Yin Soon-Sun Hong Ju-Hee Kang Jun-Kyu Suh Ji-Kan Ryu |
| author_facet | Kalyan Ghatak Guo Nan Yin Soon-Sun Hong Ju-Hee Kang Jun-Kyu Suh Ji-Kan Ryu |
| author_sort | Kalyan Ghatak |
| collection | DOAJ |
| description | Purpose: Diabetes mellitus, one of the major causes of erectile dysfunction, leads to a poor response to phosphodiesterase-5
inhibitors. Heat shock protein 70 (Hsp70), a ubiquitous molecular chaperone, is known to play a role in cell survival and
neuroprotection. Here, we aimed to assess whether and how Hsp70 improves erectile function in diabetic mice.
Materials and Methods: Eight-week-old male C57BL/6 mice and Hsp70-Tg mice were used in this study. We injected Hsp70
protein into the penis of streptozotocin (STZ)-induced diabetic mice. Detailed mechanisms were evaluated in WT or Hsp70-
Tg mice under normal and diabetic conditions. Primary MCECs, and MPG and DRG tissues were cultivated under normalglucose
and high-glucose conditions.
Results: Using Hsp70-Tg mice or Hsp70 protein administration, we demonstrate that elevated levels of Hsp70 restores erectile
function in diabetic mice. We found that cystathionine gamma-lyase (Cse) is a novel target of Hsp70 in this process,
showing that Hsp70-Cse acts through the SDF1/HO-1/PI3K/Akt/eNOS/NF-κB p65 pathway to exert its neurovascular regeneration-
promoting effects. Coimmunoprecipitation and pull-down assays using mouse cavernous endothelial cells treated with
Hsp70 demonstrated physical interactions between Hsp70 and Cse with a dissociation constant of 1.8 nmol/L.
Conclusions: Our findings provide novel and solid evidence that Hsp70 acts through a Cse-dependent mechanism to mediate
neurovascular regeneration and restoration of erectile function under diabetic conditions. |
| first_indexed | 2024-04-11T21:25:35Z |
| format | Article |
| id | doaj.art-24b954aae037464cb5e1404ae56041e8 |
| institution | Directory Open Access Journal |
| issn | 2287-4208 2287-4690 |
| language | English |
| last_indexed | 2024-04-11T21:25:35Z |
| publishDate | 2022-10-01 |
| publisher | Korean Society for Sexual Medicine and Andrology |
| record_format | Article |
| series | The World Journal of Men's Health |
| spelling | doaj.art-24b954aae037464cb5e1404ae56041e82022-12-22T04:02:25ZengKorean Society for Sexual Medicine and AndrologyThe World Journal of Men's Health2287-42082287-46902022-10-0140458059910.5534/wjmh.210249Heat Shock Protein 70 in Penile Neurovascular Regeneration Requires Cystathionine Gamma-LyaseKalyan Ghatak0https://orcid.org/0000-0002-1589-7362Guo Nan Yin1https://orcid.org/0000-0002-2512-7337Soon-Sun Hong2https://orcid.org/0000-0001-7679-1388Ju-Hee Kang3https://orcid.org/0000-0001-5235-8993Jun-Kyu Suh4https://orcid.org/0000-0002-1812-9449Ji-Kan Ryu5https://orcid.org/0000-0003-2125-0212Inha University School of MedicineInha University School of MedicineInha UniversityInha University College of MedicineInha University School of MedicineInha University School of MedicinePurpose: Diabetes mellitus, one of the major causes of erectile dysfunction, leads to a poor response to phosphodiesterase-5 inhibitors. Heat shock protein 70 (Hsp70), a ubiquitous molecular chaperone, is known to play a role in cell survival and neuroprotection. Here, we aimed to assess whether and how Hsp70 improves erectile function in diabetic mice. Materials and Methods: Eight-week-old male C57BL/6 mice and Hsp70-Tg mice were used in this study. We injected Hsp70 protein into the penis of streptozotocin (STZ)-induced diabetic mice. Detailed mechanisms were evaluated in WT or Hsp70- Tg mice under normal and diabetic conditions. Primary MCECs, and MPG and DRG tissues were cultivated under normalglucose and high-glucose conditions. Results: Using Hsp70-Tg mice or Hsp70 protein administration, we demonstrate that elevated levels of Hsp70 restores erectile function in diabetic mice. We found that cystathionine gamma-lyase (Cse) is a novel target of Hsp70 in this process, showing that Hsp70-Cse acts through the SDF1/HO-1/PI3K/Akt/eNOS/NF-κB p65 pathway to exert its neurovascular regeneration- promoting effects. Coimmunoprecipitation and pull-down assays using mouse cavernous endothelial cells treated with Hsp70 demonstrated physical interactions between Hsp70 and Cse with a dissociation constant of 1.8 nmol/L. Conclusions: Our findings provide novel and solid evidence that Hsp70 acts through a Cse-dependent mechanism to mediate neurovascular regeneration and restoration of erectile function under diabetic conditions.cystathionine gamma-lyasediabetes mellituserectile dysfunctionheat shock protein 70neovascularizationnerve regeneration |
| spellingShingle | Kalyan Ghatak Guo Nan Yin Soon-Sun Hong Ju-Hee Kang Jun-Kyu Suh Ji-Kan Ryu Heat Shock Protein 70 in Penile Neurovascular Regeneration Requires Cystathionine Gamma-Lyase The World Journal of Men's Health cystathionine gamma-lyase diabetes mellitus erectile dysfunction heat shock protein 70 neovascularization nerve regeneration |
| title | Heat Shock Protein 70 in Penile Neurovascular Regeneration Requires Cystathionine Gamma-Lyase |
| title_full | Heat Shock Protein 70 in Penile Neurovascular Regeneration Requires Cystathionine Gamma-Lyase |
| title_fullStr | Heat Shock Protein 70 in Penile Neurovascular Regeneration Requires Cystathionine Gamma-Lyase |
| title_full_unstemmed | Heat Shock Protein 70 in Penile Neurovascular Regeneration Requires Cystathionine Gamma-Lyase |
| title_short | Heat Shock Protein 70 in Penile Neurovascular Regeneration Requires Cystathionine Gamma-Lyase |
| title_sort | heat shock protein 70 in penile neurovascular regeneration requires cystathionine gamma lyase |
| topic | cystathionine gamma-lyase diabetes mellitus erectile dysfunction heat shock protein 70 neovascularization nerve regeneration |
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