ArticleThe journal of sexual medicine2013
Activated Rho kinase mediates diabetes-induced elevation of vascular arginase activation and contributes to impaired corpora cavernosa relaxation: possible involvement of p38 MAPK activation.
Article in The journal of sexual medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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26 citing papers in PubMed, 52 citations in OpenAlex.
- Differences in adipose-derived stem cells from rats with various health statuses and their effects in diabetic rats with erectile dysfunction.Asian journal of andrology · 2026Article
- The Impact of Glucagon-like Peptide-1 Receptor Agonists on Erectile Function: Friend or Foe?Biomolecules · 2025Review
- Erectile Dysfunction in Diabetes Mellitus: A Comprehensive Narrative Review of Pathophysiology, Genetic Association Studies and Therapeutic Approaches.Endocrinology, diabetes & metabolism · 2025Review
- Molecular Mechanisms and Risk Factors Related to the Pathogenesis of Peyronie's Disease.International journal of molecular sciences · 2023Review
- Supplementation withMarine drugs · 2022Article
- Novel Therapeutics for Diabetic Retinopathy and Diabetic Macular Edema: A Pathophysiologic Perspective.Frontiers in physiology · 2022Review
- 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
- Human recombinant arginase I [HuArgI (Co)-PEG5000]-induced arginine depletion inhibits ovarian cancer cell adhesion and migration through autophagy-mediated inhibition of RhoA.Journal of ovarian research · 2021Article
- Constitutive LH receptor activity impairs NO-mediated penile smooth muscle relaxation.Reproduction (Cambridge, England) · 2021Article
- Loganin alleviates testicular damage and germ cell apoptosis induced by AGEs upon diabetes mellitus by suppressing the RAGE/p38MAPK/NF-κB pathway.Journal of cellular and molecular medicine · 2020Article
- Liraglutide Ameliorates Erectile DysfunctionFrontiers in pharmacology · 2020Article
- Potential Therapeutic Role of Dietary Supplementation withOxidative medicine and cellular longevity · 2020Article
- Hyperglycemia-impaired aortic vasorelaxation mediated through arginase elevation: Role of stress kinase pathways.European journal of pharmacology · 2019Article
- Mechanisms of Diabetes-Induced Endothelial Cell Senescence: Role of Arginase 1.International journal of molecular sciences · 2018Article
- Arginase: A Multifaceted Enzyme Important in Health and Disease.Physiological reviews · 2018Review
- Activation of the NGF/TrkA signaling pathway attenuates diabetic erectile dysfunction.Oncotarget · 2017Article
- Biphasic Effect of Diabetes on Neuronal Nitric Oxide Release in Rat Mesenteric Arteries.PloS one · 2016Article
- Article
- Tissue-specific up-regulation of arginase I and II induced by p38 MAPK mediates endothelial dysfunction in type 1 diabetes mellitus.British journal of pharmacology · 2015Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
introductionActivated RhoA/Rho kinase (ROCK) has been implicated in diabetes-induced erectile dysfunction. Earlier studies have demonstrated involvement of ROCK pathway in the activation of arginase in endothelial cells. However, signaling pathways activated by ROCK in the penis remain unclear.
aimWe tested whether ROCK and p38 MAPK are involved in the elevation of arginase activity and subsequent impairment of corpora cavernosal (CC) relaxation in diabetes.
methodsEight weeks after streptozotocin-induced diabetes, vascular functional studies, arginase activity assay, and protein expression of RhoA, ROCK, phospho-p38 MAPK, p38 MAPK, phospho-MYPT-1(Thr850), MYPT-1 and arginase levels were assessed in CC tissues from nondiabetic wild type (WT), diabetic (D) WT (WT + D), partial ROCK 2(+/-) knockout (KO), and ROCK 2(+/-) KO + D mice.
main outcome measuresThe expression of RhoA, ROCK 1 and 2, phosphorylation of MYPT-1(Thr850) and p38 MAPK, arginase activity/expression, endothelial- and nitrergic-dependent relaxation of CC was assayed.
resultsDiabetes significantly reduced maximum relaxation (Emax ) to both endothelium-dependent acetylcholine (WT + D: Emax; 61 ± 4% vs. WT: Emax; 75 ± 2%) and nitrergic nerve stimulation. These effects were associated with increased expression of active RhoA, ROCK 2, phospho-MYPT-1(Thr850), phospho-p38 MAPK, arginase II, and activity of corporal arginase (1.6-fold) in WT diabetic CC. However, this impairment in CC of WT + D mice was absent in heterozygous ROCK 2(+/-) KO + D mice for acetylcholine (Emax : 80 ± 5%) and attenuated for nitrergic nerve-induced relaxation. CC of ROCK 2(+/-) KO + D mice showed much less ROCK activity, did not exhibit p38 MAPK activation, and had reduced arginase activity and arginase II expression. These findings indicate that ROCK 2 mediates diabetes-induced elevation of arginase activity. Additionally, pretreatment of WT diabetic CC with inhibitors of arginase (ABH) or p38 MAPK (SB203580) partially prevented impairment of ACh- and nitrergic nerve-induced relaxation and elevation of arginase activity.
conclusionROCK 2, p38 MAPK and arginase play key roles in diabetes-induced impairment of CC relaxation.
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