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- Title
Heat Shock Protein 70 in Penile Neurovascular Regeneration Requires Cystathionine Gamma-Lyase.
- Authors
Ghatak, Kalyan; Guo Nan Yin; Soon-Sun Hong; Ju-Hee Kang; Jun-Kyu Suh; Ji-Kan Ryu
- Abstract
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.
- Subjects
DIABETES; IMPOTENCE; PHOSPHODIESTERASE-5 inhibitors; HEAT shock proteins; CYSTATHIONINE gamma-lyase
- Publication
World Journal of Men's Health, 2022, Vol 40, Issue 4, p580
- ISSN
2287-4208
- Publication type
Article
- DOI
10.5534/wjmh.210249