Short time exposure to hypoxia promotes H9c2 cell growth

Takahashi, Rie; Kawawa, Akiyuki; Kubota, Shunichiro

doi:10.1016/j.bbagen.2006.06.006

Cited by 6 publications

(10 citation statements)

References 18 publications

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“…In the present study, hypoxia-induced ROS generation initiated signaling via phosphorylation events, leading to a transient and early increase in MAPKs such as p38 MAPK and SAPK/JNK. MAP kinases have been shown to be activated by hypoxia and ischemia and may play an important role in the adaptive response to hypoxia (9,31,32). We observed a transient and early increase in the p38 MAPK and SAPK/JNK levels under hypoxic conditions.…”

Section: Discussionmentioning

confidence: 66%

Role of FAK phosphorylation in hypoxia-induced hMSCS migration: involvement of VEGF as well as MAPKS and eNOS pathways

Lee

Song

Ahn

et al. 2010

American Journal of Physiology-Cell Physiology

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Here we show that the effect of hypoxia on human umbilical cord blood mesenchymal stem cell (hMSC) migration is via the modulation of focal adhesion kinase (FAK) and its related signaling pathways. Hypoxia increased hMSC migration and cell viability, whereas lactate dehydrogenase (LDH) release was not affected for up to 48 h (data not shown). In addition, hypoxia increased the level of reactive oxygen species (ROS) generation in a time-dependent manner. Hypoxia-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and stress-activated protein kinase/c-Jun NH(2)-terminal kinase (SAPK/JNK) were inhibited by the antioxidant (N-acetylcysteine, NAC, 10(-6) M) and (taurine, 4x10(-6) M). Hypoxia-induced endothelial nitric oxide synthase (eNOS) phosphorylation was regulated by p38 MAPK and SAPK/JNK activation. In addition, hypoxia increased the level of hypoxia inducible factor (HIF)-1alpha expression, which was blocked by inhibition of eNOS. Also, hypoxia-induced expression of Flk-1, vascular endothelial growth factor (VEGF), and its secreted form were inhibited by HIF-1alpha small interfering RNA (siRNA). In this hypoxic condition, FAK and Src phosphorylation were increased in a time-dependent manner. Inhibition of Src with specific inhibitor (PP2, 10(-8) M) blocked hypoxia-induced FAK activation. Subsequently, hypoxia-induced FAK phosphorylation was blocked by VEGF siRNA. Finally, hypoxia-induced increase of hMSC migration was inhibited by FAK siRNA. The results indicate that hypoxia increases migration of hMSCs via VEGF-mediated FAK phospholylation and involves the cooperative activity of the ROS, MAPK, eNOS and HIF-1alpha pathways.

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Section: Discussionmentioning

confidence: 66%

Role of FAK phosphorylation in hypoxia-induced hMSCS migration: involvement of VEGF as well as MAPKS and eNOS pathways

Lee

Song

Ahn

et al. 2010

American Journal of Physiology-Cell Physiology

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“…We recently reported that although hypoxia for short time (15 min) protected H9c2 cell death, longer exposure (longer than 1 h) to hypoxia induced cell death (30). Hypoxia is known to induce apoptosis via mitochondrial intrinsic pathway.…”

Section: Effect Of Prohibitin-overexpression On Hypoxia-induced Cell mentioning

confidence: 99%

“…We further investigated the levels of Bcl-2 family (Bax and Bcl-2), as Bcl-2 maintains mitochondrial membrane potential by enhancing H + efflux in the presence of mitochondrial membrane potential-loss-inducing stimuli (28). We understand molecular mechanism of cell response to hypoxia (30). We have successfully identified prohibitin as a survival factor of H9c2 cardiomyocyte cell by using proteomics analysis.…”

Section: Effects Of Prohibitin Overexpressin On Bcl-2 and Bax Expressmentioning

confidence: 99%

“…However, little is known about the effect of prohibitin on cardiomyocytes under hypoxic stress. In the present study we have tried to identify specific proteins involved in H9c2 cell survival to better understand the molecular mechanism of cell response to hypoxia (30). We have successfully identified prohibitin as a H9c2 cardiomyocyte cell survival factor by using proteomics analysis.…”

mentioning

confidence: 99%

“…While many signaling pathways to respond to hypoxia for long time were reported (1,2,4,17,31), little information is available concerning signaling pathways to respond to hypoxia for short time. We recently demonstrated that short time exposure to hypoxia (15 min) in H9c2 cardiomyocytes protected cells against cell death (30). Cardiomyocytes undergo apoptosis following release of cytochrome c from mitochondria to the cytosol in hypoxic condition.…”

mentioning

confidence: 99%

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Prohibitin protects against hypoxia-induced H9c2 cardiomyocyte cell death

2010

Self Cite

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We recently demonstrated that short time exposure to hypoxia (15 min) in H9c2 cardiomyocytes protected cells against cell death, and longer exposure to hypoxia induced cell death. To understand the molecular mechanism concerning cell death and survival, it is intriguing to identify survival factors against cell death. Using proteomics analysis, levels of proteins derived from H9c2 cells exposed to hypoxia and normoxia were compared and candidates for survival factor were identified. One of the candidates was a prohibitin. Overexpression of prohibitin inhibited H9c2 cell death induced by hypoxia for longer hours. We further clarified the mechanism of cell death. Overexpression of prohibitin inhibited decrease of mitochondrial membrane potential levels, decrease of Bcl-2 level in mitochondria and cytochrome c release to cytosol from mitochondria induced by hypoxia. The mechanism for survival was that overexpression of prohibitin inhibited cytochrome c release by decrease of mitochondrial membrane potential levels and decrease of Bcl-2 level. Taken together, identified prohibitin may function as a survival factor against hypoxiainduced cell death.

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A potential mechanism for short time exposure to hypoxia‐induced DNA synthesis in primary cultured chicken hepatocytes: Correlation between Ca²⁺/PKC/MAPKs and PI3K/Akt/mTOR

Lee

Han

2008

J of Cellular Biochemistry

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Less information is available concerning the molecular mechanisms of cell survival after hypoxia in hepatocytes. Therefore, this study examined the effect of hypoxia on DNA synthesis and its related signal cascades in primary cultured chicken hepatocytes. Hypoxia increased [3H] thymidine incorporation, which was increased significantly after 0-24 h of hypoxic exposure. Indeed, the percentage of cell population in the S phase was increased in hypoxia condition. However, the release of LDH indicating cellular injury was not changed under hypoxic conditions. Hypoxia increased Ca2+ uptake and PKC translocation from the cytosol to the membrane fraction. Among the PKC isoforms, hypoxia stimulated the translocation of PKC alpha and epsilon. Hypoxia also phosphorylated the p38 and p44/42 mitogen-activated protein kinases (MAPKs), which were blocked by the inhibition of PKC. On the other hand, hypoxia increased Akt and mTOR phosphorylation, which was blocked in the absence of intra/extracellular Ca2+. The inhibition of PKC/MAPKs or PI3K/Akt pathway blocked the hypoxia-induced [3H] thymidine incorporation. However, hypoxia-induced Ca2+ uptake and PKC translocation was not influenced by LY 294002 or Akt inhibitor and hypoxia-induced MAPKs phosphorylation was not changed by rapamycin. In addition, LY 294002 or Akt inhibitor has no effect on the phosphorylation of MAPKs. It suggests that there is no direct interaction between the two pathways, which cooperatively mediated cell cycle progression to hypoxia in chicken hepatocytes. Hypoxia also increased the level of the cell cycle regulatory proteins [cyclin D(1), cyclin E, cyclin-dependent kinase (CDK) 2, and CDK 4] and p-RB protein but decreased the p21 and p27 expression levels, which were blocked by inhibitors of upstream signal molecules. In conclusion, short time exposure to hypoxia increases DNA synthesis in primary cultured chicken hepatocytes through cooperation of Ca2+/PKC, p38 MAPK, p44/42 MAPKs, and PI3K/Akt pathways.

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Short time exposure to hypoxia promotes H9c2 cell growth

Cited by 6 publications

References 18 publications

Role of FAK phosphorylation in hypoxia-induced hMSCS migration: involvement of VEGF as well as MAPKS and eNOS pathways

Role of FAK phosphorylation in hypoxia-induced hMSCS migration: involvement of VEGF as well as MAPKS and eNOS pathways

Prohibitin protects against hypoxia-induced H9c2 cardiomyocyte cell death

A potential mechanism for short time exposure to hypoxia‐induced DNA synthesis in primary cultured chicken hepatocytes: Correlation between Ca²⁺/PKC/MAPKs and PI3K/Akt/mTOR

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Short time exposure to hypoxia promotes H9c2 cell growth

Cited by 6 publications

References 18 publications

Role of FAK phosphorylation in hypoxia-induced hMSCS migration: involvement of VEGF as well as MAPKS and eNOS pathways

Role of FAK phosphorylation in hypoxia-induced hMSCS migration: involvement of VEGF as well as MAPKS and eNOS pathways

Prohibitin protects against hypoxia-induced H9c2 cardiomyocyte cell death

A potential mechanism for short time exposure to hypoxia‐induced DNA synthesis in primary cultured chicken hepatocytes: Correlation between Ca2+/PKC/MAPKs and PI3K/Akt/mTOR

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A potential mechanism for short time exposure to hypoxia‐induced DNA synthesis in primary cultured chicken hepatocytes: Correlation between Ca²⁺/PKC/MAPKs and PI3K/Akt/mTOR