Cellular Stress and Molecular Responses in Bladder Ischemia

• Published in: International journal of molecular sciences 2021-11, Vol.22 (21), p.11862
• Main Authors: Yang, Jing-Hua, Choi, Han-Pil, Niu, Wanting, Azadzoi, Kazem M
• Format: Article
• Language: English
• Subjects: Adenosine kinase; Adenosine monophosphate; Aging; AMP-Activated Protein Kinases - metabolism; Antioxidants; Apoptosis; Arteriosclerosis; Atherosclerosis; Bladder; bladder ischemia; Cardiovascular disease; Caspase 3 - metabolism; Caspase-3; cellular stress; Cellular stress response; Erectile dysfunction; Free radicals; Gene Expression Regulation; Growth factors; Heat shock proteins; Homeostasis; Humans; Hypertension; Hypoxia-inducible factors; Ischemia; Ischemia - metabolism; MAP kinase; Metabolism; Muscle contraction; Muscles; Nerve growth factor; Neurodegeneration; non-coded amino acids; Oxidative stress; Post-translation; post-translational modifications; Protein kinase; Review; Risk factors; Sensors; Smooth muscle; Therapeutic targets; Transforming growth factor-b; Urinary Bladder - metabolism; Urinary Bladder - pathology; Urinary tract; Urogenital system; Vascular endothelial growth factor; Vein & artery diseases
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222111862

The concept of bladder ischemia as a contributing factor to detrusor overactivity and lower urinary tract symptoms (LUTS) is evolving. Bladder ischemia as a consequence of pelvic arterial atherosclerosis was first documented in experimental models and later in elderly patients with LUTS. It was shown that early-stage moderate ischemia produces detrusor overactivity, while prolonged severe ischemia provokes changes consistent with detrusor underactivity. Recent studies imply a central role of cellular energy sensors, cellular stress sensors, and stress response molecules in bladder responses to ischemia. The cellular energy sensor adenosine monophosphate-activated protein kinase was shown to play a role in detrusor overactivity and neurodegeneration in bladder ischemia. The cellular stress sensors apoptosis signal-regulating kinase 1 and caspase-3 along with heat shock proteins were characterized as important contributing factors to smooth muscle structural modifications and apoptotic responses in bladder ischemia. Downstream pathways seem to involve hypoxia-inducible factor, transforming growth factor beta, vascular endothelial growth factor, and nerve growth factor. Molecular responses to bladder ischemia were associated with differential protein expression, the accumulation of non-coded amino acids, and post-translational modifications of contractile proteins and stress response molecules. Further insight into cellular stress responses in bladder ischemia may provide novel diagnostic and therapeutic targets against LUTS.