Sphingosine-1-phosphate inhibits H2O2-induced granulosa cell apoptosis via the PI3K/Akt signaling pathway

Nakahara, Tsutomu; Iwase, Akira; Nakamura, Tomoko; Kondo, Mio; Bayasula,; Kobayashi, Hiroharu; Takikawa, Sachiko; Manabe, Shuichi; Goto, Maki; Kotani, Tomomi; Kikkawa, Fumitaka

doi:10.1016/j.fertnstert.2012.06.008

Cited by 78 publications

(58 citation statements)

References 40 publications

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“…Z-VAD almost completely inhibited caspase3 cleavage. These results suggest that H 2 O 2 can induce apoptosis in ovarian granulosa cells, which was consistent with the previous studies [17]. Since Bcl-2 family proteins are the major regulators of apoptosis, we determine how Bcl-2 family members are involved in granulosa cell apoptosis induced by H 2 O 2 .…”

Section: Discussionsupporting

confidence: 91%

Oxidative stress-induced apoptosis in granulosa cells involves JNK, p53 and Puma

et al. 2017

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Reactive oxygen species (ROS) play important roles in follicular development and survival. Granulosa cell death is associated with increased ROS, but the mechanism of granulosa cell death induced by ROS is not clear. In order to define the molecular link between ROS and granulosa cell death, COV434, human granulosa tumor cells, were treated with H2O2. Compared to control cells, H2O2 induced granulosa cell death in a dose- and time-dependent manner. H2O2 induced an increase in Bax, Bak and Puma, and a decrease in anti-apoptotic molecules such as Bcl-2, Bcl-xL and Mcl-1. Both knockdown of Puma and overexpression of Bcl-xL could inhibit H2O2-induced granulosa cell death. These results suggest that suppression of Puma and overexpression of anti-apoptotic Bcl-2 family members could improve granulosa cell survival. To explore the mechanisms responsible for these findings, ROS in granulosa cells treatment with H2O2 were measured. The results showed that ROS was increased in a H2O2 dose- and time-dependent manner at the earlier time point. In addition, H2O2 induced an increase in Nrf2 and phosphorylation of JNK and p53. SP600125, an inhibitor of JNK, inhibits H2O2-induced phosphorylation of JNK and p53, and granulosa cell death. Antioxidant N-acetylcysteine (NAC) dose-dependently prevents H2O2-induced granulosa cell death. Furthermore, NAC also prevents phosphorylation of JNK and p53 induced by H2O2. Taken together, these data suggest that H2O2 regulates cell death in granulosa cells via the ROS-JNK-p53 pathway. These findings provide an improved understanding of the mechanisms underlying granulosa cell apoptosis, which could potentially be useful for future clinical applications.

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Section: Discussionsupporting

confidence: 91%

Oxidative stress-induced apoptosis in granulosa cells involves JNK, p53 and Puma

et al. 2017

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“…These events protect against translocation of the pro-apoptotic proteins from the cytosol to the mitochondria and reduce cell death. Several studies have found that S1P, synthesized by Sphk1, is responsible for promoting pro-survival processes through PI3K/Akt [27,31,35]. Here we demonstrated that inhibition of Sphks/S1P formation by SKI II reduced PI3K/Akt phosphorylation on Serine 473 and reduced its activity.…”

Section: Discussionsupporting

confidence: 53%

Original article The key role of sphingosine kinases in the molecular mechanism of neuronal cell survival and death in an experimental model of Parkinson’s disease

Pyszko¹,

Strosznajder²

2014

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“…The detrimental effects of oxidative stress, particularly DNA damage, are involved in ageing, degenerative diseases and cancer [5]. In human granulosa cells, treatment with H 2 O 2 increases the percentage of apoptotic cells in a dose-dependent manner and increases the levels of activated caspase-3 [20]. In the present study, our results also showed that treatment of COV434 cells with H 2 O 2 caused DNA damage and induced apoptosis on the basis of the increase in the caspase-3/-7 activity levels, exposure of PS in the cell membrane, nuclear fragmentation, pyknosis and visible cell shrinkage, which are typical of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…However, oxidative stress induced by reactive oxygen species (ROS) causes cellular damage related to ageing [7], which leads to apoptosis of granulosa cells [6, 12]. Subsequently, apoptosis of granulosa cells leads to follicular atresia [14, 20]. Thus, fol‍licles decline gradually with ageing and disappear completely at the time of menopause.…”

Section: Introductionmentioning

confidence: 99%

3,4-Dihydroxybenzaldehyde Derived from <i>Prunus mume</i> Seed Inhibits Oxidative Stress and Enhances Estradiol Secretion in Human Ovarian Granulosa Tumor Cells

Kono

Nomura

Okuno

et al. 2014

Acta Histochem. Cytochem.

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Granulosa cells form ovarian follicles and play important roles in the growth and maturation of oocytes. The protection of granulosa cells from cellular injury caused by oxidative stress is an effective therapy for female infertility. We here investigated an effective bioactive compound derived from Prunus mume seed extract that protects granulosa cells from hydrogen peroxide (H2O2)-induced apoptosis. We detected the bioactive compound, 3,4-dihydroxybenzaldehyde (3,4-DHBA), via bioactivity-guided isolation and found that it inhibited the H2O2-induced apoptosis of granulosa cells. We also showed that 3,4-DHBA promoted estradiol secretion in granulosa cells and enhanced the mRNA expression levels of steroidogenic factor 1, a promoter of key steroidogenic enzymes. These results suggest that P. mume seed extract may have clinical potential for the prevention and treatment of female infertility.

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Sphingosine-1-phosphate inhibits H2O2-induced granulosa cell apoptosis via the PI3K/Akt signaling pathway

Cited by 78 publications

References 40 publications

Oxidative stress-induced apoptosis in granulosa cells involves JNK, p53 and Puma

Oxidative stress-induced apoptosis in granulosa cells involves JNK, p53 and Puma

Original article The key role of sphingosine kinases in the molecular mechanism of neuronal cell survival and death in an experimental model of Parkinson’s disease

3,4-Dihydroxybenzaldehyde Derived from <i>Prunus mume</i> Seed Inhibits Oxidative Stress and Enhances Estradiol Secretion in Human Ovarian Granulosa Tumor Cells

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