ArticleThe journal of sexual medicine2011
Extracellular signal-regulated kinase (ERK) inhibition decreases arginase activity and improves corpora cavernosal relaxation in streptozotocin (STZ)-induced diabetic mice.
Article in The journal of sexual medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 30 citations in OpenAlex.
- Erectile Dysfunction in Diabetes Mellitus: A Comprehensive Narrative Review of Pathophysiology, Genetic Association Studies and Therapeutic Approaches.Endocrinology, diabetes & metabolism · 2025Review
- Methylglyoxal-Modified Albumin Effects on Endothelial Arginase Enzyme and Vascular Function.Cells · 2023Article
- Arginase: Biological and Therapeutic Implications in Diabetes Mellitus and Its Complications.Oxidative medicine and cellular longevity · 2022Review
- Crosstalk of TLR4, vascular NADPH oxidase, and COVID-19 in diabetes: What are the potential implications?Vascular pharmacology · 2021Review
- Macrophage-Specific Toll Like Receptor 9 (TLR9) Causes Corpus Cavernosum Dysfunction in Mice Fed a High Fat Diet.The journal of sexual medicine · 2021Article
- Angiotensin (1-7) Inhibits Ang II-mediated ERK1/2 Activation by Stimulating MKP-1 Activation in Vascular Smooth Muscle Cells.International journal of molecular and cellular medicine · 2020Article
- Article
- Hyperglycemia-impaired aortic vasorelaxation mediated through arginase elevation: Role of stress kinase pathways.European journal of pharmacology · 2019Article
- Influence of arginase polymorphisms and arginase levels/activity on the response to erectile dysfunction therapy with sildenafil.The pharmacogenomics journal · 2018Article
- Metformin treatment improves erectile function in an angiotensin II model of erectile dysfunction.The journal of sexual medicine · 2013Article
Corrections and comments
- Erratum issuedErratum.2015
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
introductionIncreased arginase activity (AA) has been implicated in hypertension and diabetes-induced endothelial dysfunction by reducing L-arginine availability and nitric oxide production. Higher levels of active extracellular signal-regulated kinase (ERK) have been found in patients with erectile dysfunction (ED) compared to patients without it. Both ERK and arginase have been reported to affect the expression and activity of nitric oxide synthase (NOS) and consequently penile erection. Nevertheless, signaling pathways activated by ERK in the penis are not well known.
aimWe hypothesized that inhibition of ERK by ERK inhibitor PD98059 decreases AA and thus improves cavernosal relaxation in streptozotocin (STZ)-diabetic mice.
methodsThe AA, ERK, eNOS, and arginase I and II expressions were examined through Western blot, and functional response of cavernosal tissue were determined. Control and diabetic cavernosal tissues were pretreated with PD98059 (10(-5) M) and arginase inhibitor ((S)-(2-boronoethyl)-L-cysteine hydrochloride, [BEC]10(-4) M]).
main outcome measuresDiabetes increased AA significantly (twofold) over control mice and this effect was blocked by acute treatment with PD98059. Cavernosal strips from diabetic mice exhibited decreased relaxation (STZ-diabetic vs. control, respectively) to both the endothelium-dependent agonist acetylcholine (38.0 ± 5% vs. 82.5 ± 7%) and nitrergic stimulation (27 ± 2% vs. 76 ± 6%) by electrical field stimulation (EFS, 1-32 Hz). However, this impairment in cavernosal relaxation from diabetic mice was attenuated by treatment with PD98059 in nitrergic (27 ± 2% vs. 60 ± 4%) and endothelium-dependent relaxation responses (38.0 ± 5% vs. 67.5 ± 6%). Acute treatment with the arginase inhibitor BEC (10(-4) M) also improves EFS-induced relaxation in diabetic mice (31 ± 3% vs. 49 ± 2%). Moreover, vascular expression of activated ERK was increased in diabetic over control mice.
conclusionThese data suggest that ERK inhibition prevents elevation of penile AA and protects against ED caused by diabetes.
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