The possible role of liver kinase <scp>B</scp>1 in hydroquinone‐induced toxicity of murine fetal liver and bone marrow hematopoietic stem cells

Li, Zhen; Wang, Chunhong; Zhu, Jie; Bai, Yinjuan; Wang, Wei; Zhou, Yanfeng; Zhang, Shaozun; Liu, Xiangxiang; Zhou, Sheng; Huang, Wenting; Bi, Yang; Wang, Hong

doi:10.1002/tox.22094

Cited by 8 publications

(6 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…LKB1 plays an important role in the generation and activity of mature T cells . In hematopoietic stem cells, LKB1 serves as an essential agent to preserve the viability, modulate quiescence and metabolic homeostasis, and monitor energy metabolism and cell cycles . Furthermore, several studies using tissue‐specific LKB1 knockout murine models have showed that LKB1 is crucial to the pool of primordial follicles .…”

mentioning

confidence: 99%

RETRACTED: LKB1 suppresses androgen synthesis in a mouse model of hyperandrogenism via IGF‐1 signaling

Gao

Huang

et al. 2019

FEBS Open Bio

View full text Add to dashboard Cite

Polycystic ovary syndrome (PCOS) is a major cause of anovulatory sterility in women, and most PCOS patients exhibit hyperandrogenism (HA). Liver kinase b1 (LKB1) is a tumor suppressor that has recently been reported to be involved in PCOS. However, the mechanism by which LKB1 affects HA has not previously been elucidated. We report here that ovarian LKB1 levels are significantly decreased in a female mouse model of HA. Moreover, we report that LKB1 expression is inhibited by elevated androgens via activation of androgen receptors. In addition, LKB1 treatment was observed to suppress androgen synthesis in theca cells and promote estrogen production in granulosa cells by regulating steroidogenic enzyme expression. As expected, LKB1 knockdown inhibited estrogen levels and enhanced androgen levels, and LKB1‐transgenic mice were protected against HA. The effect of LKB1 appears to be mediated via IGF‐1 signaling. In summary, we describe here a key role for LKB1 in controlling sex hormone levels.

show abstract

mentioning

confidence: 99%

RETRACTED: LKB1 suppresses androgen synthesis in a mouse model of hyperandrogenism via IGF‐1 signaling

Gao

Huang

et al. 2019

FEBS Open Bio

View full text Add to dashboard Cite

show abstract

“…Previous studies have revealed that different doses of HQ may induce apoptosis ( 24 , 25 ). Treatment with a low dose of HQ for 24 h induced HQ-mediated apoptosis in murine fetal livers and bone marrow hematopoietic cells ( 24 ). Treatment with a high dose of HQ for 24 h promoted apoptosis in bone marrow-derived mesenchymal stem cells ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

PARP-1 may be involved in hydroquinone-induced apoptosis by poly ADP-ribosylation of ZO-2

Liu

Yuan

Ling

et al. 2017

Molecular Medicine Reports

View full text Add to dashboard Cite

Hydroquinone (HQ), a major reactive metabolite of benzene, contributes to benzene-induced leukemia. The molecular mechanisms that underlie this activity remain to be elucidated. Poly ADP-ribosylation (PARylation) is a type of reversible posttranslational modification that is performed by enzymes in the PAR polymerase (PARP) family and mediates different biological processes, including apoptosis. Zona occludens 2 (ZO-2) is a tight junction scaffold protein, which is involved in cell proliferation and apoptosis. The present study investigated the activity and mechanisms regulated by PARP-1 during HQ-induced apoptosis using TK6 lymphoblastoid cells and PARP-1-silenced TK6 cells. The results revealed that exposure to 10 µM HQ for 72 h induced apoptosis in TK6 cells and that apoptosis was attenuated in PARP-1-silenced TK6 cells. In cells treated with HQ, inhibition of PARP-1 increased the expression of B cell leukemia/lymphoma 2 (Bcl-2), increased ATP production and reduced reactive oxygen species (ROS) production relative to the levels observed in cells treated with HQ alone. Co-localization of ZO-2 and PAR (or PARP-1 protein) was determined using immunofluorescence confocal microscopy. The findings of the present study revealed that ZO-2 was PARylated via an interaction with PARP-1, which was consistent with an analysis of protein expression that was performed using western blot analysis, which determined that ZO-2 protein expression was upregulated in HQ-treated control cells and downregulated in HQ-treated PARP-1-silenced TK6 cells. These findings indicated that prolonged exposure to a low dose of HQ induced TK6 cells to undergo apoptosis, whereas inhibiting PARP-1 attenuates cellular apoptosis by activating Bcl-2 and energy-saving processes and reducing ROS. The present study determined that PARP-1 was involved in HQ-induced apoptosis by PARylation of ZO-2.

show abstract

“…Benzene, one of the earliest industrial chemicals, has been demonstrated to affect the health of a large number of workers 1,2 and can lead to tumor formation, such as acute myeloid leukemia and aplastic anemia, through occupational exposure. Hydroquinone (HQ), also known as one of the main metabolites of benzene in vivo, plays an important role in the toxicity effect of benzene 3–7 . HQ has been shown to cause DNA damage, such as double‐strand breaks (DSBs), 8 chromosomal aberration, 9 sister chromatid exchange, 10 and genomic instability, 11 in cultured human and animal cells and expression changes in ncRNAs, such as long noncoding RNAs (lncRNAs) 12 and small noncoding RNAs (miRNAs) 13 .…”

Section: Introductionmentioning

confidence: 99%

Hsa_circ_0001944 regulates apoptosis by regulating the binding of PARP1 and HuR in leukemia and malignant transformed cells induced by hydroquinone

Zhong

Ling

Meng

et al. 2022

Environmental Toxicology

View full text Add to dashboard Cite

Hydroquinone (HQ) is one of the major metabolites of benzene and can cause abnormal gene expression. It is a known carcinogen that alters cell cycle disruption and cell proliferation. However, its chemical mechanism remain a mystery. Circular RNAs (cir-cRNAs) are a subtype of noncoding RNAs (ncRNAs) that play a variety of roles in biological processes. Hsa_circ_001944 expression was upregulated in 30 leukemia patients and HQ-induced malignant transformed TK6 cells. Hsa_circ_001944 silencing inhibited the growth of HQ-TK6 cells and halted the cell cycle. The silencing of hsa_circ_0001944 led to increased cell accumulation in G1 versus S phase, increased apoptosis in the sh1944 versus the shNC group, and increased levels of DNA damage (γ-H2AX), leading to cell cycle arrest. In summary, inhibition of hsa_circ_001944 restricted cell growth by inhibiting cell cycle arrest and induced growth of HQ-TK6 cells by modulating PARP1 expression. Hsa_circ_0001944 targeted HuR, which is a kind of RNA-binding protein, to control PARP1 expression via RNAinter, RBPmap, and RBPdb. Fluorescence in situ hybridization combined with immunofluorescent labeling and western blotting experiments showed that hsa_circ_001944 was able to dissociate HuR and PARP1 binding in HQ-TK6 cells, control PARP1 production, and ultimately alter the PARP1/H-Ras pathway.

show abstract

The possible role of liver kinase B1 in hydroquinone‐induced toxicity of murine fetal liver and bone marrow hematopoietic stem cells

Cited by 8 publications

References 49 publications

RETRACTED: LKB1 suppresses androgen synthesis in a mouse model of hyperandrogenism via IGF‐1 signaling

RETRACTED: LKB1 suppresses androgen synthesis in a mouse model of hyperandrogenism via IGF‐1 signaling

PARP-1 may be involved in hydroquinone-induced apoptosis by poly ADP-ribosylation of ZO-2

Hsa_circ_0001944 regulates apoptosis by regulating the binding of PARP1 and HuR in leukemia and malignant transformed cells induced by hydroquinone

Contact Info

Product

Resources

About