AKR1B1 Represses Glioma Cell Proliferation through p38 MAPK-Mediated Bcl-2/BAX/Caspase-3 Apoptotic Signaling Pathways

Chang, Kun-Che; Li, Chia-Yang; Lieu, Ann-Shung; Lin, Chih‐Lung

doi:10.3390/cimb45040222

Cited by 15 publications

(4 citation statements)

References 63 publications

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“…Based on their roles, members of the Bcl-2 family can be divided into three groups: pro-apoptotic proteins Bax, pro-apoptotic activators like NOXA and PUMA, and anti-apoptotic proteins Bcl-2 [43,44]. Bcl-2 binds to Bax and interacts to prevent mitochondrial pore formation, thereby inhibiting the execution of cell apoptosis [45,46]. In this study, we found that PEDV infection can promote the expression of p53 in IPEC-J2 cells at 18 h post-infection.…”

Section: Discussionmentioning

confidence: 99%

Isolation and Identification of a Tibetan Pig Porcine Epidemic Diarrhoea Virus Strain and Its Biological Effects on IPEC-J2 Cells

Li,

Wang,

et al. 2024

IJMS

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Porcine epidemic diarrhoea virus (PEDV) is a coronavirus that can cause severe watery diarrhoea in piglets, with high morbidity and mortality rates, seriously hindering the healthy development of the global swine industry. In this study, we isolated a strain of PEDV from Tibetan pigs and named it CH/GS/2022. Subsequently, we screened the apoptosis signals of PEDV-infected IPEC-J2 cells and studied the correlation between apoptosis signals and cell apoptosis. The results showed that different infections of PEDV induced different degrees of apoptosis in cells, and PEDV-induced cell apoptosis was dose-dependent. We then detected the expression of the p53, p38, JNK, Bax, and Bcl-2 genes in the apoptosis signal pathway. The results showed that 24 h after PEDV infection, the expression of the p53, p38, JNK, and Bax genes in IPEC-J2 cells increased significantly, while the expression of the Bcl-2 gene decreased significantly (p < 0.05). Subsequently, we used Western blot to detect the protein levels of these five genes, and the results showed that PEDV infection upregulated the expression of p53, p38, JNK, and Bax proteins (p < 0.05) while downregulating the expression of Bcl-2 protein (p < 0.05). Thus, it was initially inferred that PEDV infection could regulate cell apoptosis by activating the p53, p38, and JNK signalling pathways. Finally, we further investigated the apoptosis of the cells through the use of inhibitors. The results indicated that the p53 inhibitor Pifithrin-α has a significant inhibitory effect on the expression of the p53 protein after PEDV infection and can reverse the expression levels of Bax and Bcl-2 proteins. This suggested that p53 is involved in PEDV-induced cell apoptosis. Similarly, the p38 MAPK inhibitor SB203580 has an inhibitory effect on the expression of the p38 protein and can reverse the expression levels of Bax and Bcl-2 proteins. This suggested that p38 is also involved in PEDV-induced cell apoptosis. On the other hand, the JNK inhibitor SP600125 has no inhibitory effect on the expression of the JNK protein after PEDV infection, but the expression levels of Bax and Bcl-2 proteins have changed. Furthermore, it is noteworthy that SP600125 can inhibit the activity of apoptotic proteins but not their levels, resulting in reduced cell apoptosis. These preliminary results indicated that JNK may be involved in PEDV-induced IPEC-J2 cell apoptosis.

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Section: Discussionmentioning

confidence: 99%

Isolation and Identification of a Tibetan Pig Porcine Epidemic Diarrhoea Virus Strain and Its Biological Effects on IPEC-J2 Cells

Li,

Wang,

et al. 2024

IJMS

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“…p38 MAPK is activated in response to various stress signals, including DNA damage, oxidative stress, and cytokines. Once activated, p38 MAPK can induce cell cycle arrest ( Faust et al, 2012 ) or apoptosis ( Huang et al, 2023 ), effectively eliminating potentially cancerous cells. Furthermore, p38 MAPK signaling initiates G1 mitotic arrest not only in cancer cells but also in a variety of terminally differentiated cell types ( Perdiguero et al, 2007 ; Molnár et al, 1997 ; Xiu et al, 2003 ).…”

Section: Discussionmentioning

confidence: 99%

“…Bcl-x, a member of the Bcl-2 family, and Bax proteins regulate the survival and apoptosis of mouse PGCs during embryogenesis ( Rucker et al, 2000 ), and a subpopulation of migrating PGCs are positive for phosphorylated p38 MAPK protein ( Figure 1E ). As p38 MAPK-induced BAX/Bcl-2/caspase-3 apoptosis signaling is involved in glioma cell proliferation ( Huang et al, 2023 ), p38 MAPK may play a pivotal role in controlling PGCs output by eliminating damaged or unscheduled pluripotency expression through mediation with Bcl-x and Bax proteins. In considering another potential role of p38 MAPK in reprogramming, it is noteworthy that the PI3K-Akt signaling pathway is highly activated in cEGLCs and that they are more strongly dependent on its signaling than conventional EGCs in maintaining undifferentiated state ( Figures 4B,C ).…”

Section: Discussionmentioning

confidence: 99%

p38 MAPK as a gatekeeper of reprogramming in mouse migratory primordial germ cells

Okamura,

Kohara,

Chigi

et al. 2024

Front. Cell Dev. Biol.

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Mammalian germ cells are derived from primordial germ cells (PGCs) and ensure species continuity through generations. Unlike irreversible committed mature germ cells, migratory PGCs exhibit a latent pluripotency characterized by the ability to derive embryonic germ cells (EGCs) and form teratoma. Here, we show that inhibition of p38 mitogen-activated protein kinase (MAPK) by chemical compounds in mouse migratory PGCs enables derivation of chemically induced Embryonic Germ-like Cells (cEGLCs) that do not require conventional growth factors like LIF and FGF2/Activin-A, and possess unique naïve pluripotent-like characteristics with epiblast features and chimera formation potential. Furthermore, cEGLCs are regulated by a unique PI3K-Akt signaling pathway, distinct from conventional naïve pluripotent stem cells described previously. Consistent with this notion, we show by performing ex vivo analysis that inhibition of p38 MAPK in organ culture supports the survival and proliferation of PGCs and also potentially reprograms PGCs to acquire indefinite proliferative capabilities, marking these cells as putative teratoma-producing cells. These findings highlight the utility of our ex vivo model in mimicking in vivo teratoma formation, thereby providing valuable insights into the cellular mechanisms underlying tumorigenesis. Taken together, our research underscores a key role of p38 MAPK in germ cell development, maintaining proper cell fate by preventing unscheduled pluripotency and teratoma formation with a balance between proliferation and differentiation.

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“…Furthermore, P38 MAPK pathway has been evidenced to mediate apoptosis [43]. Studies have shown that phosphorylated P38 MAPK can activate caspase-3 and promote apoptosis by downregulating Bcl-2 [44][45][46]. Thereby, VK2 reduced lung cell apoptosis by inhibiting LPS-induced activation of P38 MAPK.…”

Section: Discussionmentioning

confidence: 99%

Vitamin K2 (MK-7) attenuates LPS-induced acute lung injury via inhibiting inflammation, apoptosis, and ferroptosis

Wang,

Yang,

Liu

et al. 2023

PLoS ONE

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Acute lung injury (ALI) is a life-threatening disease that has received considerable critical attention in the field of intensive care. This study aimed to explore the role and mechanism of vitamin K2 (VK2) in ALI. Intraperitoneal injection of 7 mg/kg LPS was used to induce ALI in mice, and VK2 injection was intragastrically administered with the dose of 0.2 and 15 mg/kg. We found that VK2 improved the pulmonary pathology, reduced myeloperoxidase (MPO) activity and levels of TNF-α and IL-6, and boosted the level of IL-10 of mice with ALI. Moreover, VK2 played a significant part in apoptosis by downregulating and upregulating Caspase-3 and Bcl-2 expressions, respectively. As for further mechanism exploration, we found that VK2 inhibited P38 MAPK signaling. Our results also showed that VK2 inhibited ferroptosis, which manifested by reducing malondialdehyde (MDA) and iron levels, increasing glutathione (GSH) level, and upregulated and downregulated glutathione peroxidase 4 (GPX4) and heme oxygenase-1 (HO-1) expressions, respectively. In addition, VK2 also inhibited elastin degradation by reducing levels of uncarboxylated matrix Gla protein (uc-MGP) and desmosine (DES). Overall, VK2 robustly alleviated ALI by inhibiting LPS-induced inflammation, apoptosis, ferroptosis, and elastin degradation, making it a potential novel therapeutic candidate for ALI.

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AKR1B1 Represses Glioma Cell Proliferation through p38 MAPK-Mediated Bcl-2/BAX/Caspase-3 Apoptotic Signaling Pathways

Cited by 15 publications

References 63 publications

Isolation and Identification of a Tibetan Pig Porcine Epidemic Diarrhoea Virus Strain and Its Biological Effects on IPEC-J2 Cells

Isolation and Identification of a Tibetan Pig Porcine Epidemic Diarrhoea Virus Strain and Its Biological Effects on IPEC-J2 Cells

p38 MAPK as a gatekeeper of reprogramming in mouse migratory primordial germ cells

Vitamin K2 (MK-7) attenuates LPS-induced acute lung injury via inhibiting inflammation, apoptosis, and ferroptosis

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