Hypoxia induces apoptosis and autophagic cell death in human periodontal ligament cells through <scp>HIF</scp>‐1α pathway

Song, Ziliang; Zhou, Wen‐Jie; Ran, Shu; Ni, Jun

doi:10.1111/j.1365-2184.2012.00810.x

Cited by 74 publications

(71 citation statements)

References 51 publications

(51 reference statements)

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“…Our results revealed that CoCl 2 generated a hypoxic condition and induced autophagy by increasing levels of HIF-1α, BNIP3, PI3KC3 and autophagosomal marker LC3-II in CCA cell lines. A chemical mimetic of hypoxia CoCl 2 increased autophagy has been demonstrated in several models such as in the H9c2 rat cardiomyoblast cell culture (Gallo et al, 2014) and human periodontal ligament cells (Song et al, 2012) resulting in an increasing LC3-II level that is similar to O 2 depletion induced hypoxia (Hu et al, 2012). The hypoxia induced LC3-II/LC3-I ratio has been shown that it activates autophagosome maturation (Gallo et al, 2014).…”

Section: Discussionmentioning

confidence: 96%

High Expression of HIF-1α, BNIP3 and PI3KC3: Hypoxia-Induced Autophagy Predicts Cholangiocarcinoma Survival and Metastasis

Thongchot

Yongvanit²,

Loilome³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Hypoxia and autophagy are known to facilitate tumor progression. We here aimed to investigate the role of hypoxia-associated autophagy in cholangiocarcinoma (CCA) survival and metastasis. Immunostaining of hypoxicresponsive proteins (HIF-1α and BNIP3) and a key regulator of autophagy (PI3KC3) were examined in CCA tissues and their expression levels were compared with clinicopathological parameters. A hypoxia mimicking condition (CoCl 2 treatment) was also tested regarding CCA cell functions. Our results showed that HIF-1α (66%), BNIP3 (44%) and PI3KC3 (46%) showed strong staining in human CCA tissues. Positive expression of HIF-1α (p=0.033), BNIP3 (p=0.040) and PI3KC3 (p=0.037) was significantly correlated with lymph node metastasis. HIF-1α was well associated with BNIP3 (r=0.3, p<0.01) and PI3KC3 (r=0.2, p<0.01). The survival rates of patients who were positive with HIF-1α (p=0.047) or co-expressed HIF-1α and BNIP3 (p=0.032) or HIF-1α and PI3KC3 (p=0.043) were significantly greater than in the negative groups. CCA cells treated with CoCl 2 showed an increase in HIF-1α, BNIP3, PI3KC3 and LC3-II, with increased cell migration and pFAK levels. These data suggest that hypoxia associated autophagy enhances CCA metastasis, resulting in a poor prognosis of CCA.

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Section: Discussionmentioning

confidence: 96%

High Expression of HIF-1α, BNIP3 and PI3KC3: Hypoxia-Induced Autophagy Predicts Cholangiocarcinoma Survival and Metastasis

Thongchot

Yongvanit²,

Loilome³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…Research into the relationship between hippocampal apoptosis and hypoxia might reveal the potential mechanism of epilepsy. Since HIF-1α is a key marker of hypoxia, and hypoxia is an important mediator for apoptosis (Song et al, 2012), recent studies have focused on HIF-1a and its significance to epilepsy (Gualtieri et al, 2013;Peng et al, 2013). However, to our knowledge, there is little research into the influence of HIF-1α on the hippocampal apoptosis in the epileptic model.…”

Section: Discussionmentioning

confidence: 98%

“…In fact, the significance of HIF-1α on apoptosis has been investigated by numerous studies of pro-and anti-apoptotic processes (Carmeliet et al, 1998, Song et al, 2012 and hypoxemia can temporally decrease oxygen delivery during seizures (Bateman et al, 2008). Here, HIF-1α may be a cellular response during epileptogenesis.…”

Section: Introductionmentioning

confidence: 97%

Hypoxia inducible factor-1α expression is associated with hippocampal apoptosis during epileptogenesis

et al. 2014

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“…On the other hand, it is reported that extreme hypoxia-like response induced by the chemical cobalt chloride (CoCl 2 ) could stimulate periodontal ligament (PDL) stem cell cytotoxicity through mitochondria-apoptotic and autophagic pathways involving HIF-1α [17]. During pathological processes, it is reported that a low oxygen level may regulate cell migration of oral cancer cells, thus inluencing the invasion and metastasis in malignant oral lesions [18].…”

Section: Hypoxia In the Oral/periodontal Environmentmentioning

confidence: 99%

Role of the Hypoxia-Inducible Factor in Periodontal Inflammation

Wang¹,

Chen²,

Leung³

2017

Hypoxia and Human Diseases

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Human periodontitis is a chronic inlammatory disease induced by opportunistic Gramnegative anaerobic bacteria at the tooth-supporting apparatus. Within the gingivitisafected sulcus or periodontal pocket, the resident anaerobic bacteria interact with the host inlammatory reactions leading to a lower oxygen or hypoxic environment. A cellular/tissue oxygen-sensing mechanism and its appropriate regulation are needed to assist tissue adaptation to natural/pathology-induced variations in oxygen availability. In this chapter, we reviewed the biological relevance of hypoxia in periodontal/oral cellular development, epithelial barrier function, periodontal inlammation, and immunity. The role of hypoxia-inducible factor-1α in pathogen-host cross talk and alveolar bone homeostasis was also discussed. The naturally occurring pathophysiological process of hypoxia appeared to entail fundamental relevance for periodontal defense and regeneration.

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Hypoxia induces apoptosis and autophagic cell death in human periodontal ligament cells through HIF‐1α pathway

Abstract: Our data showed that CoCl(2) could induce cytotoxicity through mitochondria- apoptotic and autophagic pathways involved in HIF-1α. CoCl(2 -treated PDLCs may serve as an in vitro model for studies of molecular mechanisms in periodontitis.

Cited by 74 publications

References 51 publications

High Expression of HIF-1α, BNIP3 and PI3KC3: Hypoxia-Induced Autophagy Predicts Cholangiocarcinoma Survival and Metastasis

High Expression of HIF-1α, BNIP3 and PI3KC3: Hypoxia-Induced Autophagy Predicts Cholangiocarcinoma Survival and Metastasis

Hypoxia inducible factor-1α expression is associated with hippocampal apoptosis during epileptogenesis

Role of the Hypoxia-Inducible Factor in Periodontal Inflammation

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