&lt;p&gt;Regulation of Cellular Stress Signaling in Bladder Ischemia&lt;/p&gt;

Yang, Jinghua; Li, Yedan; Azad, Roya; Azadzoi, Kazem M.

doi:10.2147/rru.s271618

Cited by 5 publications

(32 citation statements)

References 30 publications

(99 reference statements)

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“…Ischemia engenders metabolic stress and provokes cellular stress responses in the bladder [ 41 , 42 ]. Stressed cells coordinate protective responses against the ischemic insult to rebalance the compromised energy homeostasis.…”

Section: Stress Response Molecules In Bladder Ischemiamentioning

confidence: 99%

“…Interruption of energy resources to the cells activates cellular stress response molecules and cell danger signals to prevent structural damage and promote cell function [ 43 , 44 ]. However, the subcellular consequences of ischemic stress depend on the severity of nutrient deficiency, the level of hypoxia, the extent of oxidative insult, and the cell’s ability to respond to the stress-eliciting rudiments [ 41 , 42 , 43 , 44 ]. The initial ramifications of ischemic stress involve the upregulation of stress response molecules followed by cell danger signaling and survival responses [ 41 , 42 ].…”

Section: Stress Response Molecules In Bladder Ischemiamentioning

confidence: 99%

“…However, the subcellular consequences of ischemic stress depend on the severity of nutrient deficiency, the level of hypoxia, the extent of oxidative insult, and the cell’s ability to respond to the stress-eliciting rudiments [ 41 , 42 , 43 , 44 ]. The initial ramifications of ischemic stress involve the upregulation of stress response molecules followed by cell danger signaling and survival responses [ 41 , 42 ]. Three major stress response molecules have been characterized in the ischemic bladder.…”

Section: Stress Response Molecules In Bladder Ischemiamentioning

confidence: 99%

“…ASK1 is upregulated in rat bladder ischemia, suggesting the activation of metabolic stress and redox sensing in the ischemic bladder tissue. The upregulation of ASK1 seems to provoke apoptotic activity and degenerative responses in the ischemic bladder ( Figure 5 ) [ 42 ]. The exposure of human bladder smooth muscle cells to hypoxia upregulates ASK1 in a manner similar to that of bladder ischemia, suggesting the regulation of ASK1 expression by hypoxia under ischemic conditions ( Figure 5 ) [ 42 ].…”

Section: Stress Response Molecules In Bladder Ischemiamentioning

confidence: 99%

“…The upregulation of ASK1 seems to provoke apoptotic activity and degenerative responses in the ischemic bladder ( Figure 5 ) [ 42 ]. The exposure of human bladder smooth muscle cells to hypoxia upregulates ASK1 in a manner similar to that of bladder ischemia, suggesting the regulation of ASK1 expression by hypoxia under ischemic conditions ( Figure 5 ) [ 42 ]. The upregulation of ASK1 in bladder ischemia and hypoxic smooth muscle cells is associated with morphological changes consistent with apoptotic degenerative responses, including cell shrinkage, fragmentation and condensation of the nucleus, partial disruption of the nuclear membrane, chromatin condensation, increased cytoplasmic and nuclear ribosomes, and the degradation of mitochondrial granules ( Figure 5 ).…”

Section: Stress Response Molecules In Bladder Ischemiamentioning

confidence: 99%

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Cellular Stress and Molecular Responses in Bladder Ischemia

Yang

Choi

Niu

et al. 2021

IJMS

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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.

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Section: Stress Response Molecules In Bladder Ischemiamentioning

confidence: 99%

Section: Stress Response Molecules In Bladder Ischemiamentioning

confidence: 99%

Section: Stress Response Molecules In Bladder Ischemiamentioning

confidence: 99%

Section: Stress Response Molecules In Bladder Ischemiamentioning

confidence: 99%

Section: Stress Response Molecules In Bladder Ischemiamentioning

confidence: 99%

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Cellular Stress and Molecular Responses in Bladder Ischemia

Yang

Choi

Niu

et al. 2021

IJMS

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Pathophysiological Mechanisms Involved in Overactive Bladder/Detrusor Overactivity

Chess-Williams

Sellers

2023

Curr Bladder Dysfunct Rep

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Purpose of Review To examine the latest published findings on the pathophysiological mechanisms involved in the development of overactive bladder (OAB) and detrusor overactivity (DO), and to identify common pathways linked to the risk factors associated with these conditions. Recent Findings Evidence is accumulating, both clinical and experimental, that many of the factors linked to the development of OAB/DO, including ageing, bladder outlet obstruction, psychological stress, and obesity are associated with reduced bladder blood flow. This induces local tissue inflammation with cytokine release and enhanced oxidative stress, ultimately resulting in altered detrusor sensitivity, detrusor hypertrophy and fibrosis, together with afferent hypersensitivity. These mechanisms would explain the symptoms of urgency and frequency observed in OAB patients. Although not a characteristic of OAB, undetected low level bacterial infections of the bladder have been proposed to explain the OAB symptoms in patients resistant to standard treatments. In this condition, inflammatory responses without reductions in perfusion activate the inflammatory pathways. Summary Evidence is mounting that poor bladder perfusion and local inflammatory responses are central mechanisms involved in the development of OAB/DO. As our understanding of these pathophysiological mechanisms advances, new avenues for drug development will be identified and ultimately treatment may become more individualized depending on the particular pathway involved and the drugs available.

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Formation of Double Stranded RNA Provokes Smooth Muscle Contractions and Structural Modifications in Bladder Ischemia

Yang¹,

Zhao²,

Niu³

et al. 2022

RRU

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Purpose Growing evidence suggests that ischemia provokes detrusor overactivity and degenerative responses in the bladder. Underlying mechanisms appear to involve modification of smooth muscle contractile rudiments by hypoxia, redox, cellular stress and cell survival signaling. Downstream pathways of cellular stress and stress response molecules eliciting bladder dysfunction in ischemia remain largely elusive. Our goal was to define the role of double stranded RNA (dsRNA), a stress response molecule provoked by redox, in ischemia mediated bladder dysfunction. Methods A rat model of pelvic ischemia along with a cell culture hypoxia model were used to investigate the expression levels, functional consequences, structural aspects, and regulatory mechanisms of dsRNA in the bladder. Gene and protein expression were examined by reverse transcription polymerase chain reaction (RT-PCR), dot blot, and Western blotting, respectively. Tissue structure and function were assessed using histological staining and organ bath. Regulatory mechanisms were analyzed in cultured bladder smooth muscle cells. Results The data presented here provide the first evidence of the formation of dsRNA in the overactive bladder. dsRNA is a cellular stress response molecule that sensitizes smooth muscle and regulates inflammatory and degenerative rejoinders. Our data suggest that the production of dsRNA in the bladder is provoked by ischemia. Formation of dsRNA appears to augment bladder smooth muscle contractions and provoke fibrotic and apoptotic responses. Downstream actions of dsRNA in the bladder may involve upregulation of dsRNA-activated protein kinase R (PKR) and caspase-3, the executioner of apoptosis. Conclusion Activation of dsRNA/PKR pathway may play a role in sensitization of bladder smooth muscle cells to contractile stimuli, whereas dsRNA and caspase-3 crosstalk appear to modulate cellular stress and instigate degenerative responses in bladder ischemia. These observations suggest the role of dsRNA in bladder dysfunction and may open new perspectives to overcome overactive smooth muscle contractions and structural damage in the bladder.

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<p>Regulation of Cellular Stress Signaling in Bladder Ischemia</p>

Cited by 5 publications

References 30 publications

Cellular Stress and Molecular Responses in Bladder Ischemia

Cellular Stress and Molecular Responses in Bladder Ischemia

Pathophysiological Mechanisms Involved in Overactive Bladder/Detrusor Overactivity

Formation of Double Stranded RNA Provokes Smooth Muscle Contractions and Structural Modifications in Bladder Ischemia

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