Activation of the intrinsic mitochondrial apoptotic pathway in swine influenza virus-mediated cell death

Choi, Young Ki; Kim, Tae‐Kyung; Kim, Chul-Joong; Lee, Joong-Seob; Oh, Se‐Young; Joo, Heesoo; Foster, Douglas N.; Hong, Ki-Chang; You, Seungkwon; Kim, Hyunggee

doi:10.1038/emm.2006.2

Cited by 22 publications

(12 citation statements)

References 25 publications

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“…Several studies have reported that Bcl-2 modulates cell differentiation (Lu et al, 1995) and gene expression (Miyashita et al, 1995) and also regulates the transactivity of several transcription factors such as NF-κB (Ricca et al, 2000), and p53 (Froesch et al,199). Furthermore Bcl-2 regulates outer mitochondrial membrane permeability and release of cytochrome C and other apoptogenic factors (Huang and Strasser, 2000;Adams and Cory, 2001;Newmeyer and Ferguson-Miller, 2003;Tsujimoto, 2003;Choi et al, 2006). Previously, we reported that PA produced by PLD raises Bcl-2 protein expression in several cells lines (Oh et al, 2007;Cho et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Members of the Bcl-2 family are classified as antiapoptotic factors, which include Bcl-2, Bcl-xL, Mcl-1, and others. The proapoptotic members can be separated into two subgroups: the Bax subfamily (Bax, Bak and Bok), which contain multiple BH domains, and the BH3-only family including Bad, Bid, Bim, Noxa, Hrk, and others (Huang and Strasser, 2000;Adams and Cory, 2001;Newmeyer and Ferguson-Miller, 2003;Tsujimoto, 2003;Choi et al, 2006). Bcl-2 protein is the most important regulator of apoptosis and is involved in the regulation of the cell cycle (O'Reilly et al, 1997), prolongs cell survival (Korsmeyer, 1992), and inhibits apoptosis (O'Reilly et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

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STAT3 is involved in phosphatidic acid-induced Bcl-2 expression in HeLa cells

et al. 2009

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Phosphatidic acid (PA), the product of a PLD-mediated reaction, is a lipid second messenger that participates in various intracellular signaling events and is known to regulate a growing list of signaling proteins. We found that Bcl-2 was upregulated by PA treatment in HeLa cells. However, how PA upregulates Bcl-2 expression has not yet been studied. In this study, we tried to discover the mechanisms of

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

STAT3 is involved in phosphatidic acid-induced Bcl-2 expression in HeLa cells

et al. 2009

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“…While several of the isolates tested showed a significantly enhanced ability to induce apoptosis compared to that after treatment with gemcitabine and cisplatin, the H7N3 isolate repeatedly outperformed the others in terms of the rapidity and potency of cell death induced. Strain-specific variations in apoptotic induction have previously been documented in primary cultures and established cell lines in the cases of human, avian, and swine influenza viruses (36,37). The particularity of the H7N3 isolate led us to investigate it further; we examined the specific apoptotic pathway induced in a highly sensitive cell line (BxPC-3) compared to that of a resistant line (HPDE6).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, although the pancreas is not considered a typical site of replication after standard infection, influenza A virus seems to be capable of infecting and damaging pancreatic cells in severe infections. Furthermore, the fact that IAV is known to induce apoptosis in numerous cell types (35)(36)(37) may provide an advantage in overcoming the known resistance to apoptosis of PDA cells.…”

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confidence: 99%

Oncolytic Activity of Avian Influenza Virus in Human Pancreatic Ductal Adenocarcinoma Cell Lines

Kasloff

Pizzuto

Silic-Benussi

et al. 2014

J Virol

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Pancreatic ductal adenocarcinoma (PDA) is the most lethal form of human cancer, with dismal survival rates due to late-stage diagnoses and a lack of efficacious therapies. Building on the observation that avian influenza A viruses (IAVs) have a tropism for the pancreas in vivo, the present study was aimed at testing the efficacy of IAVs as oncolytic agents for killing human PDA cell lines. Receptor characterization confirmed that human PDA cell lines express the alpha-2,3-and the alpha-2,6-linked glycan receptor for avian and human IAVs, respectively. PDA cell lines were sensitive to infection by human and avian IAV isolates, which is consistent with this finding. Growth kinetic experiments showed preferential virus replication in PDA cells over that in a nontransformed pancreatic ductal cell line. Finally, at early time points posttreatment, infection with IAVs caused higher levels of apoptosis in PDA cells than gemcitabine and cisplatin, which are the cornerstone of current therapies for PDA. In the BxPC-3 PDA cell line, apoptosis resulted from the engagement of the intrinsic mitochondrial pathway. Importantly, IAVs did not induce apoptosis in nontransformed pancreatic ductal HPDE6 cells. Using a model based on the growth of a PDA cell line as a xenograft in SCID mice, we also show that a slightly pathogenic avian IAV significantly inhibited tumor growth following intratumoral injection. Taken together, these results are the first to suggest that IAVs may hold promise as future agents of oncolytic virotherapy against pancreatic ductal adenocarcinomas. IMPORTANCEDespite intensive studies aimed at designing new therapeutic approaches, PDA still retains the most dismal prognosis among human cancers. In the present study, we provide the first evidence indicating that avian IAVs of low pathogenicity display a tropism for human PDA cells, resulting in viral RNA replication and a potent induction of apoptosis in vitro and antitumor effects in vivo. These results suggest that slightly pathogenic IAVs may prove to be effective for oncolytic virotherapy of PDA and provide grounds for further studies to develop specific and targeted viruses, with the aim of testing their efficacy in clinical contexts.

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“…Immunoprecipitation was performed as follows (29). After homogenizing liver tissue with 1 ml of lysis buffer (pH 7.5, 50 M Tris-HCl, 150 M NaCl, 1 M MgCl 2 , 1 M CaCl 2 , 1 M sodium orthovanadate, 100 M NaF, 1 M EGTA, 1% Triton X-100, 10% glycerol, leupeptin (5 µg/ml) and 1 mmol/l phenylmethylsulfonyl fluoride) on ice, it was washed twice with ice-cold PBS.…”

Section: Methodsmentioning

confidence: 99%

Human umbilical cord blood-derived mesenchymal stem cells improve glucose homeostasis in rats with liver cirrhosis

Jung

Uhm²,

Lim³

et al. 2011

Int J Oncol

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Abstract. Disturbance of glucose metabolism is a common feature in liver cirrhosis which is associated with insulin resistance and is an established risk factor for disease progression and survival in patients with chronic liver diseases. We investigated whether umbilical cord blood-derived mesenchymal stem cells (HMSCs) have an effect on the expression of molecules responsible for glucose utilization and hepatic gluconeogenesis, focusing on the insulin signaling pathway in rats with liver cirrhosis. Rats received a dose of CCl 4 (100 µl/100 g 4:1 in corn oil) thrice-weekly. HMSCs were infused at 4 weeks after induction of liver cirrhosis by CCl 4 . Infusion of HMSCs improved insulin resistance which was associated with increased glucose levels and decreased insulin sensitivity in CCl 4 -induced cirrhotic rats. HMSCs increased activities in the proximal part of the insulin signaling cascade, as evidenced by increased expression of key enzymes such as phosphatidylinositol-3-kinase (PI 3-kinase), protein kinase B (PKB), protein kinase C-ζ (PKC-ζ), and the decrease of glycogen synthase kinase 3 (GSK-3) compared to CCl 4 -induced liver cirrhotic rats. We also observed that glucose-6-phosphatase (G-6-P) and phosphoenolpyruvate kinase (PEPCK), two hepatic enzymes involved in gluconeogenesis were strongly decreased over 40-50% after infusion of HMSCs. Taken together, our results showed that HMSCs could improve insulin resistance in CCl 4 -induced liver cirrhosis, thereby contributing to glucose homeostasis.

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Activation of the intrinsic mitochondrial apoptotic pathway in swine influenza virus-mediated cell death

Abstract: The mitochondrial pathway of swine influenza virus (SIV)-induced apoptosis was investigated using porcine kidney (PK-15) cells, swine testicle (

Cited by 22 publications

References 25 publications

STAT3 is involved in phosphatidic acid-induced Bcl-2 expression in HeLa cells

STAT3 is involved in phosphatidic acid-induced Bcl-2 expression in HeLa cells

Oncolytic Activity of Avian Influenza Virus in Human Pancreatic Ductal Adenocarcinoma Cell Lines

Human umbilical cord blood-derived mesenchymal stem cells improve glucose homeostasis in rats with liver cirrhosis

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