Novel quinazoline HMJ-30 induces U-2 OS human osteogenic sarcoma cell apoptosis through induction of oxidative stress and up-regulation of ATM/p53 signaling pathway

Background. Serine hydroxymethyltransferase 2 (SHMT2) activity ensures that cells have a survival advantage in ischemic conditions and regulates redox homeostasis. In this study, we aimed to investigate the role of SHMT2 after hepatic ischemia-reperfusion (IR), which involves hypoxia, ischemic conditions, and cell apoptosis. Methods. A 70% IR model was established in C57BL/6J mice with or without SHMT2 knockdown. H&E staining, liver weight/body weight, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels and cell apoptosis were tested to analyze liver damage and function. Then, the related cellular signals were probed. Results. The level of SHMT2 protein was significantly increased at 24 h and 48 h after IR (p<0.001). Mice in the shSHMT2 group showed more necrotic areas and histological damage at 24 h (p<0.01) after IR and higher levels of serum ALT and AST (p<0.05) compared with those of mice in the scramble group. After IR for 24 h, the expression of TUNEL in the shSHMT2 group was significantly higher than that in the scramble group, as shown by histological analysis (p<0.01). Mechanistically, the JNK/P53 signaling pathway was activated by IR, and knockdown of SHMT2 exacerbated hepatocyte apoptosis. Conclusions. Knockdown of SHMT2 worsens IR injury through the ROS/JNK/P53 signaling pathway. Our discovery expands the understanding of both molecular and metabolic mechanisms involved in IR. SHMT2 is a possible therapeutic target to improve the prognosis of liver transplantation (LT) and subtotal hepatectomy.

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PPM1D Knockdown Suppresses Cell Proliferation, Promotes Cell Apoptosis, and Activates p38 MAPK/p53 Signaling Pathway in Acute Myeloid Leukemia

Technology in Cancer Research & Treatment ◽

10.1177/1533033820942312 ◽

2020 ◽

Vol 19 ◽

pp. 153303382094231

Author(s):

Bin Li ◽

Jie Hu ◽

Di He ◽

Qi Chen ◽

Suna Liu ◽

...

Keyword(s):

Cell Proliferation ◽

Acute Myeloid Leukemia ◽

Signaling Pathway ◽

P38 Mapk ◽

Protein Phosphatase ◽

Cell Apoptosis ◽

Myeloid Leukemia ◽

P53 Signaling ◽

P53 Signaling Pathway ◽

Acute Myeloid

Objectives: This study was to explore the effect of protein phosphatase, Mg2+/Mn2+ dependent 1D knockdown on proliferation and apoptosis as well as p38 MAPK/p53 signaling pathway in acute myeloid leukemia. Methods: The expression of protein phosphatase, Mg2+/Mn2+ dependent 1D was detected in acute myeloid leukemia cell lines including SKM-1, KG-1, AML-193, and THP-1 cells, and normal bone marrow mononuclear cells isolated from healthy donors. The knockdown of protein phosphatase, Mg2+/Mn2+ dependent 1D was conducted by transfecting small interfering RNA into AML-193 cells and KG-1 cells. Results: The relative messenger RNA/protein expressions of protein phosphatase, Mg2+/Mn2+ dependent 1D were higher in SKM-1, KG-1, AML-193, and THP-1 cells compared with control cells (normal bone marrow mononuclear cells). After transfecting protein phosphatase, Mg2+/Mn2+ dependent 1D small interfering RNA into AML-193 cells and KG-1 cells, both messenger RNA and protein expressions of protein phosphatase, Mg2+/Mn2+ dependent 1D were significantly reduced, indicating the successful transfection. Most importantly, knockdown of protein phosphatase, Mg2+/Mn2+ dependent 1D suppressed cell proliferation and promoted cell apoptosis in AML-193 cells and KG-1 cells. In addition, knockdown of protein phosphatase, Mg2+/Mn2+ dependent 1D enhanced the expressions of p-p38 and p53 in AML-193 cells and KG-1 cells. The above observation suggested that protein phosphatase, Mg2+/Mn2+ dependent 1D knockdown suppressed cell proliferation, promoted cell apoptosis, and activated p38 MAPK/p53 signaling pathway in acute myeloid leukemia cells. Conclusion: Protein phosphatase, Mg2+/Mn2+ dependent 1D is implicated in acute myeloid leukemia carcinogenesis, which illuminates its potential role as a treatment target for acute myeloid leukemia.

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Multiple transcriptomic profiling: p53 signaling pathway is involved in DEHP-induced prepubertal testicular injury via promoting cell apoptosis and inhibiting cell proliferation of Leydig cells

Journal of Hazardous Materials ◽

10.1016/j.jhazmat.2020.124316 ◽

2020 ◽

pp. 124316

Author(s):

Junke Wang ◽

Tianxin Zhao ◽

Jiadong Chen ◽

Lian Kang ◽

Yuexin Wei ◽

...

Keyword(s):

Cell Proliferation ◽

Signaling Pathway ◽

Cell Apoptosis ◽

Leydig Cells ◽

Transcriptomic Profiling ◽

P53 Signaling ◽

Testicular Injury ◽

P53 Signaling Pathway

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Parthenolide regulates oxidative stress‐induced mitophagy and suppresses apoptosis through p53 signaling pathway in C2C12 myoblasts

Journal of Cellular Biochemistry ◽

10.1002/jcb.28839 ◽

2019 ◽

Vol 120 (9) ◽

pp. 15695-15708 ◽

Cited By ~ 2

Author(s):

Yinghui Ren ◽

Yan Li ◽

Jienv Lv ◽

Xiangdong Guo ◽

Jieyou Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Signaling Pathway ◽

C2c12 Myoblasts ◽

P53 Signaling ◽

P53 Signaling Pathway

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Doxycycline Induces Apoptosis of Brucella Suis S2 Strain-Infected HMC3 Microglial Cells by Activating Calreticulin-Dependent JNK/p53 Signaling Pathway

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.640847 ◽

2021 ◽

Vol 11 ◽

Author(s):

Zhao Wang ◽

Yanbai Wang ◽

Huan Yang ◽

Jiayu Guo ◽

Zhenhai Wang

Keyword(s):

Protein Expression ◽

Signaling Pathway ◽

Cell Apoptosis ◽

Human Brucellosis ◽

Protein Levels ◽

P53 Signaling ◽

Brucella Suis ◽

The Central Nervous System ◽

Infected Cells ◽

P53 Signaling Pathway

Neurobrucellosis is a chronic complication of human brucellosis that is caused by the presence of Brucella spp in the central nervous system (CNS) and the inflammation play a key role on the pathogenesis. Doxycycline (Dox) is a widely used antibiotic that induces apoptosis of bacteria-infected cells. However, the mechanisms of Brucella inhibition of microglial apoptosis and Dox induction of apoptosis are still poorly understood. In this study, we found that Brucella suis S2 strain (B. suis S2) increased calreticulin (CALR) protein levels and inhbited HMC3 cell apoptosis. Hence, we constructed two HMC3 cell line variants, one with stable overexpression (HMC3-CALR) and one with low expression of CALR (HMC3-sh-CALR). CALR was found to decrease levels of p-JNK and p-p53 proteins, as well as suppress apoptosis in HMC3 cells. These findings suggest that CALR suppresses apoptosis by inhibiting the JNK/p53 signaling pathway. Next, we treated HMC3, HMC3-CALR and HMC3-sh-CALR cell lines with B. suis S2 or Dox. Our results demonstrate that B. suis S2 restrains the JNK/p53 signaling pathway to inhibit HMC3 cell apoptosis via increasing CALR protein expression, while Dox plays the opposite role. Finally, we treated B. suis S2-infected HMC3 cells with Dox. Our results confirm that Dox induces JNK/p53-dependent apoptosis in B. suis S2-infected HMC3 cells through inhibition of CALR protein expression. Taken together, these results reveal that CALR and the JNK/p53 signaling pathway may serve as novel therapeutic targets for treatment of neurobrucellosis.

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