Hypoxic preconditioning reinforces HIF-alpha-dependent HSP70 signaling to reduce ischemic renal failure-induced renal tubular apoptosis and autophagy

Yeh, Chung Hsin; Hsu, Shih Ping; Yang, Chi‐Rei; Chien, Chiang Ting; Wang, Nai Phog

doi:10.1016/j.lfs.2009.11.022

Cited by 85 publications

(73 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It has been previously reported that Hsp70 signaling is under the control of HIF-1a expression in cells such as kidney. 40 In our study, we showed the upregulation of Hsp70 in SV of the cochlea of hypoxic C57BL/6 mice, demonstrating that it may enhance the resistance of cells of SV to hypoxia-induced apoptosis, since lower activated-caspase-3 expression was noted in these zones. These findings provide a new insight into how cells overcome hypoxic stress and survive, and also disclose a new regulatory mechanism of Hsp70 expression in auditory cells.…”

Section: Articlesupporting

confidence: 55%

Hypoxia-inducible factor 1-alpha target protein up-regulation in Hypoxic cochlear neurons is associate with aged-related hearing loss in C57BL/6 mice

Donadieu

Riva

2012

Ageing Res

View full text Add to dashboard Cite

Molecular mechanisms underlining hypoxia-induced aged-hearing loss were studied. 3-months C57BL/6 mice were subjected to four weeks of hypoxia (10% 0 2 ), whereas, controls were kept under normoxic condition for up to six months. Auditory function was explored by CAP and Preyer's reflex measurements and correlated with histological analysis of the cochlea. The presence of oxidative damage, HIF-1 responsive target genes regulation involved in cell death, inflammation and neovascularization were assessed by immunofluorescence analysis. Hypoxia was associated to severe hearing loss at 4-8 and 16 KHz and degeneration of the cochlea, with significant cell loss (30%) in the spiral ganglion, the lateral wall, and the hair cells with a basal-apical alteration gradient. This was correlated with ROS formation and HIF-1a overexpression. Cochlear degeneration was due to apoptosis via activated caspase-3, P53, Bax and Bcl-2 protein differential expression in spiral ganglion, modiolus and spiral ligament. On the other hand, Hsp70, NF-kB transcription factor pathway and inflammatory mediators (caspase-1 and TNF-a) were induced in the stria vascularis. Furthermore, a phenomenon of neovascularization was observed with significant thickening of stria vascularis and increased expression of VEGF. In total, we demonstrated that the tandem-HIF-ROS is responsible for the caspase-3 and Bax-mediated apoptosis via P53 protein accumulation in the cochlear neurons, while inflammatory response mediated by Hsp70 stress protein and NF-kB transcription factor generating a neovascularization phenomenon occurred in stria vascularis.

show abstract

Section: Articlesupporting

confidence: 55%

Hypoxia-inducible factor 1-alpha target protein up-regulation in Hypoxic cochlear neurons is associate with aged-related hearing loss in C57BL/6 mice

Donadieu

Riva

2012

Ageing Res

View full text Add to dashboard Cite

show abstract

“…The HIF target proteins have important functions in renal hemodynamics (nitric oxide synthase-2 and heme-oxygenase-1), energy metabolism (glucose transporters and glycolytic enzymes), angiogenesis (VEGF), and cell proliferation/survival (ERK activation) (52). Many molecules and signaling pathways important for preconditioning in kidneys and other organs have been linked back to HIF (53)(54)(55)(56)(57). HIF activation is increasingly being recognized as a protective measure against AKI in normal kidneys (52,58 -62).…”

Section: Pathophysiology Of Ckdmentioning

confidence: 99%

Chronic Kidney Disease

Singh

Rifkin

Blantz

2010

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Epidemiologic evidence suggests that chronic kidney disease (CKD) is a risk factor for acute kidney injury (AKI) due to the prevalence of CKD in patients who have episodes of AKI. However, the high burden of comorbidities such as age, diabetes, peripheral vascular, cardiovascular, and liver disease accompanying CKD, and the difficulties of defining AKI in the setting of CKD make these observations difficult to interpret. These comorbidities not only could alter the course of AKI but also may be the driving force behind the epidemiologic association between CKD and AKI because of systemic changes and/or increased exposure to potential nephrotoxic risks. Here, we contend that studies suggesting that CKD is a risk factor for AKI may suffer from residual confounding and reflect an overall susceptibility to illness rather than biologic susceptibility of the kidney parenchyma to injury. In support of our argument, we discuss the clinical evidence from epidemiologic studies, and the knowledge obtained from animal models on the pathophysiology of AKI and CKD, demonstrating a preconditioning influence of the previously impaired kidneys against subsequent injury. We conclude that, under careful analysis, factors apart from the inherent pathophysiology of the diseased kidney may be responsible for the increased frequency of AKI in CKD patients, and the impact of CKD on the risk and severity of AKI needs further investigation. Moreover, certain elements in the pathophysiology of a previously injured kidney may, surprisingly, bear out to be protective against AKI.

show abstract

“…Transplantation/ischemia -Autophagy stimulation during renal IR is a protective mechanism to maintain energy production during the hypoxic starvation period of ischemia and/or counteract oxidative damaged proteins and organelles during reperfusion [55][56][57][58] -Autophagy contributes to renal IR damage [59][60][61][62][63][64] -In proximal tubule-specific ATG5-and ATG7-knockout mice: autophagy is protective during renal IR [55-57] -Autophagy is considered protective when ischemic duration is short (20-40 min), but detrimental when ischemic stress is severe (40-60 min) [70] Conclusion: Opposite observations because of use of non-specific compounds, different experimental models (gender, age, sex) and varying degrees of IR stress. …”

Section: Diabetic Nephropathy (Dn)mentioning

confidence: 99%

“…However, the exact outcome of autophagy stimulation in renal IR injury is still a matter of debate. Although it may seem logical to reinforce autophagy during renal IR as a protective mechanism to maintain energy production during the hypoxic starvation period of ischemia and/or counteract oxidative damaged proteins and organelles during reperfusion [55][56][57][58], several reports have made opposite observations in which autophagy contributed to renal IR damage [59][60][61][62][63][64]. Possible reasons for these conflicting findings are likely multiple.…”

Section: Transplantation/ischemiamentioning

confidence: 99%

Autophagy in renal diseases

et al. 2015

View full text Add to dashboard Cite

Autophagy is the cell biology process in which cytoplasmic components are degraded in lysosomes to maintain cellular homeostasis and energy production. In the healthy kidney, autophagy plays an important role in the homeostasis and viability of renal cells such as podocytes and tubular epithelial cells and of immune cells. Recently, evidence is mounting that (dys)regulation of autophagy is implicated in the pathogenesis of various renal diseases, and might be an attractive target for new renoprotective therapies. In this review, we provide an overview of the role of autophagy in kidney physiology and kidney diseases.

show abstract

Hypoxic preconditioning reinforces HIF-alpha-dependent HSP70 signaling to reduce ischemic renal failure-induced renal tubular apoptosis and autophagy

Cited by 85 publications

References 47 publications

Hypoxia-inducible factor 1-alpha target protein up-regulation in Hypoxic cochlear neurons is associate with aged-related hearing loss in C57BL/6 mice

Hypoxia-inducible factor 1-alpha target protein up-regulation in Hypoxic cochlear neurons is associate with aged-related hearing loss in C57BL/6 mice

Chronic Kidney Disease

Autophagy in renal diseases

Contact Info

Product

Resources

About