Occupancy of dipeptidyl peptidase IV activates an associated tyrosine kinase and triggers an apoptotic signal in human hepatocarcinoma cells

Gaetaniello, Lucia; Fiore, Michele; Filippo, Sergio De; Pozzi, Nicola; Tamasi, Sonia; Pignata, Claudio

doi:10.1002/hep.510270407

Cited by 38 publications

(21 citation statements)

References 32 publications

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“…Con¯icting data have recently been reported with regard to the potential role of CD26 in apoptosis. Transfection of CD26 cDNA into HIV-infected Jurkat cells protected them from apoptosis (Morimoto et al, 1994) whereas CD26-speci®c antibodies induced apoptosis of some hepatocarcinoma cell lines (Gaetaniello et al, 1998). Whether upregulation of CD26 confers on B-CLL cells a selective advantage or disadvantage remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Regulation of CD26/DPPIV gene expression by interferons and retinoic acid in tumor B cells

et al. 2000

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Section: Discussionmentioning

confidence: 99%

Regulation of CD26/DPPIV gene expression by interferons and retinoic acid in tumor B cells

et al. 2000

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“…As a dimer, this enzyme can convey information across the cell membrane in the same way as growth factors and cytokine receptors. In this line, it has already been shown that the structurally related AP-N (EC 3.4.11.2) and dipeptidylpeptidase IV (DP IV, EC 3.4.14.3) have a similar subcellular location and dimeric structure and that they are able to mediate intracellular signalling [263][264][265][266][267]. Monoclonal antibodies towards AP-N trigger both IP 3 receptor-linked Ca 2+ release and phosphorylation of the mitogen-activated protein kinases (Erk1/ 2, JNK and p38) in human monocytes [267,268].…”

Section: Modulation Of the Translocation Of Irap And Glut4mentioning

confidence: 92%

“…Signalling has also been described for dipeptidylpeptidase IV which is involved in T cell activation by potentiating the proliferative response after stimulation of the TcR/CD3 complex [263,269]. Despite the dipeptidylpeptidase IV molecule has a short cytoplasmic domain of only six amino acids, the binding of enzyme inhibitors and of certain monoclonal antibodies to the extracellular domain of this enzyme leads to the tyrosine phosphorylation of several signalling proteins and activation of mitogen-activated protein kinases in T lymphocytes (involved in its antitumour effect) as well as human hepatocarcinoma cells [265,270,271]. It was also found to mediate early phosphorylation mechanisms in non-haematopoietic cells such as hepatocarcinoma [265].…”

Section: Modulation Of the Translocation Of Irap And Glut4mentioning

confidence: 99%

Involvement of insulin-regulated aminopeptidase in the effects of the renin–angiotensin fragment angiotensin IV: a review

et al. 2007

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For decades, angiotensin (Ang) II was considered as the end product and the only bioactive peptide of the renin-angiotensin system (RAS). However, later studies revealed biological activity for other Ang fragments. Amongst those, Ang IV has drawn a lot of attention since it exerts a wide range of central and peripheral effects including the ability to enhance learning and memory recall, anticonvulsant and anti-epileptogenic properties, protection against cerebral ischemia, activity at the vascular level and an involvement in atherogenesis. Some of these effects are AT(1) receptor dependent but others most likely result from the binding of Ang IV to insulin-regulated aminopeptidase (IRAP) although the exact mechanism(s) of action that mediate the Ang IV-induced effects following this binding are until now not fully known. Nevertheless, three hypotheses have been put forward: since Ang IV is an inhibitor of the catalytic activity of IRAP, its in vivo effects might result from a build-up of IRAP's neuropeptide substrates. Second, IRAP is co-localized with the glucose transporter GLUT4 in several tissue types and therefore, Ang IV might interact with the uptake of glucose. A final and more intriguing hypothesis ascribes a receptor function to IRAP and hence an agonist role to Ang IV. Taken together, it is clear that further work is required to clarify the mechanism of action of Ang IV. On the other hand, a wide range of studies have made it clear that IRAP might become an important target for drug development against different pathologies such as Alzheimer's disease, epilepsy and ischemia.

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“…Also, Gaetaniello et al (1998) reported that inhibition of DPP-4 in human hepatoma cells suppress tyrosine kinase, leading to anti-apoptotic effects.…”

Section: Discussionmentioning

confidence: 99%

The protective effect of vildagliptin in chronic experimental cyclosporine A-induced hepatotoxicity

El-Sherbeeny

Nader

2016

Can. J. Physiol. Pharmacol.

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The study examined the effect of dipeptidyl peptidase-4 (DPP-4) inhibitor, vildagliptin in cyclosporine (CsA)-induced hepatotoxicity. Rats were divided into 4 groups treated for 28 days: control (vehicle), vildagliptin (10 mg/kg, orally), CsA( 20 mg/kg, SC) and CsA-vildagliptin group. Liver function was assessed by measuring serum levels of Aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (γGT), lactate dehydrogenase (LDH), albumin, and histopathological changes of liver were examined.Oxidative stress markers were evaluated. Assessment of nuclear factor-kappa B (NF-κB) activity in hepatic nuclear extract, serum DPP-4 and expression of Bax and Bcl2 using were also done.CsA-induced hepatotoxicity was evidenced by increase in serum levels of AST, ALT and γGT; a decrease in serum albumin and a significant alteration in hepatic architecture. Also, significant increase in thiobarbituricacid reactive substance (TBARS) and decrease in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH) levels, increased expression Bax proteins with deceased expression of Bcl2, increased hepatic activity of NF-κB, and serum DPP-4 level were observed upon CsA treatment. Vildagliptin significantly improved all altered parameters induced by CsA administration. Vildagliptin has the potential to protect the liver against CsA-induced hepatotoxicity by reducing oxidative stress, DPP-4 activity, apoptosis and inflammation.

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Occupancy of dipeptidyl peptidase IV activates an associated tyrosine kinase and triggers an apoptotic signal in human hepatocarcinoma cells

Cited by 38 publications

References 32 publications

Regulation of CD26/DPPIV gene expression by interferons and retinoic acid in tumor B cells

Regulation of CD26/DPPIV gene expression by interferons and retinoic acid in tumor B cells

Involvement of insulin-regulated aminopeptidase in the effects of the renin–angiotensin fragment angiotensin IV: a review

The protective effect of vildagliptin in chronic experimental cyclosporine A-induced hepatotoxicity

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