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Profiling of Proteins Regulated by Venlafaxine during Neural Differentiation of Human Cells.

Doh MS, Han DM, Oh DH, Kim SH, Choi MR, Chai YG - Psychiatry Investig (2015)

Bottom Line: To study the effects of venlafaxine during neural differentiation at the cellular level, we looked at its effect on protein expression and regulation mechanisms during neural differentiation.Treatment with venlafaxine decreased expression of prolyl 4-hydroxylase (P4HB), ubiquitin-conjugating enzyme E2K (HIP2) and plastin 3 (T-plastin), and up-regulated expression of growth factor beta-3 (TGF-β3), dihydropyrimidinase-like 3 (DPYSL3), and pyruvate kinase (PKM) after differentiation for 1 and 7 days.Our findings may contribute to improve understanding of molecular mechanism of venlafaxine.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Life Sciences, Hanyang University, Ansan, Republic of Korea.

ABSTRACT

Objective: Antidepressants are known to positively influence several factors in patients with depressive disorders, resulting in increased neurogenesis and subsequent relief of depressive disorders. To study the effects of venlafaxine during neural differentiation at the cellular level, we looked at its effect on protein expression and regulation mechanisms during neural differentiation.

Methods: After exposing NCCIT cell-derived EBs to venlafaxine during differentiation (1 day and 7 days), changes in protein expression were analyzed by 2-DE and MALDI-TOF MS analysis. Gene levels of proteins regulated by venlafaxine were analyzed by real-time RT-PCR.

Results: Treatment with venlafaxine decreased expression of prolyl 4-hydroxylase (P4HB), ubiquitin-conjugating enzyme E2K (HIP2) and plastin 3 (T-plastin), and up-regulated expression of growth factor beta-3 (TGF-β3), dihydropyrimidinase-like 3 (DPYSL3), and pyruvate kinase (PKM) after differentiation for 1 and 7 days. In cells exposed to venlafaxine, the mRNA expression patterns of HIP2 and PKM, which function as negative and positive regulators of differentiation and neuronal survival, respectively, were consistent with the observed changes in protein expression.

Conclusion: Our findings may contribute to improve understanding of molecular mechanism of venlafaxine.

No MeSH data available.


Related in: MedlinePlus

Regulation of protein expression networks by venlafaxine during neural differentiation of NCCIT cells. EBs were treated with 10 µM retinoic acid (RA) in the presence or absence of 10 µM venlafaxine (VEN) for either 1 or 7 days, and putative targets that were differentially regulated by VEN were analyzed using the analyze networks algorithm implemented in MetaCore. A: Network of proteins regulated by VEN after differentiation for 1 day. B: Network of proteins regulated by VEN after differentiation for 7 days. C: Network legend, red and blue circles indicate up- and down-regulated proteins, respectively.
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Figure 2: Regulation of protein expression networks by venlafaxine during neural differentiation of NCCIT cells. EBs were treated with 10 µM retinoic acid (RA) in the presence or absence of 10 µM venlafaxine (VEN) for either 1 or 7 days, and putative targets that were differentially regulated by VEN were analyzed using the analyze networks algorithm implemented in MetaCore. A: Network of proteins regulated by VEN after differentiation for 1 day. B: Network of proteins regulated by VEN after differentiation for 7 days. C: Network legend, red and blue circles indicate up- and down-regulated proteins, respectively.

Mentions: To explore the GeneGo Process Networks for proteins regulated by venlafaxine during neural differentiation, we used MetaCore database and MetaCore pathway analysis software (GeneGo Inc.). The MetaCore database is well suited for analyzing manually curated interactions and contains >90% of human proteins with known functions.26 We identified top scoring networks that were common to both venlafaxine-treated and control cells during neural differentiation (Figure 2). The highest scoring networks that were regulated by venlafaxine on differentiation for 1 day included TGF-β3, PKM, and HIP-2, which are involved in negative regulation of biological process (63.3%) and regulation of apoptosis (44.7%) (Figure 2A). Likewise, the highest scoring networks that were regulated by venlafaxine on differentiation for 7 days included damage-specific DNA binding protein 1 (DDB1), PKM, and P4HB, which are involved in response to chemical stimulus (76.0%) and regulation of biological quality (60.0%) (Figure 2B).


Profiling of Proteins Regulated by Venlafaxine during Neural Differentiation of Human Cells.

Doh MS, Han DM, Oh DH, Kim SH, Choi MR, Chai YG - Psychiatry Investig (2015)

Regulation of protein expression networks by venlafaxine during neural differentiation of NCCIT cells. EBs were treated with 10 µM retinoic acid (RA) in the presence or absence of 10 µM venlafaxine (VEN) for either 1 or 7 days, and putative targets that were differentially regulated by VEN were analyzed using the analyze networks algorithm implemented in MetaCore. A: Network of proteins regulated by VEN after differentiation for 1 day. B: Network of proteins regulated by VEN after differentiation for 7 days. C: Network legend, red and blue circles indicate up- and down-regulated proteins, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4310925&req=5

Figure 2: Regulation of protein expression networks by venlafaxine during neural differentiation of NCCIT cells. EBs were treated with 10 µM retinoic acid (RA) in the presence or absence of 10 µM venlafaxine (VEN) for either 1 or 7 days, and putative targets that were differentially regulated by VEN were analyzed using the analyze networks algorithm implemented in MetaCore. A: Network of proteins regulated by VEN after differentiation for 1 day. B: Network of proteins regulated by VEN after differentiation for 7 days. C: Network legend, red and blue circles indicate up- and down-regulated proteins, respectively.
Mentions: To explore the GeneGo Process Networks for proteins regulated by venlafaxine during neural differentiation, we used MetaCore database and MetaCore pathway analysis software (GeneGo Inc.). The MetaCore database is well suited for analyzing manually curated interactions and contains >90% of human proteins with known functions.26 We identified top scoring networks that were common to both venlafaxine-treated and control cells during neural differentiation (Figure 2). The highest scoring networks that were regulated by venlafaxine on differentiation for 1 day included TGF-β3, PKM, and HIP-2, which are involved in negative regulation of biological process (63.3%) and regulation of apoptosis (44.7%) (Figure 2A). Likewise, the highest scoring networks that were regulated by venlafaxine on differentiation for 7 days included damage-specific DNA binding protein 1 (DDB1), PKM, and P4HB, which are involved in response to chemical stimulus (76.0%) and regulation of biological quality (60.0%) (Figure 2B).

Bottom Line: To study the effects of venlafaxine during neural differentiation at the cellular level, we looked at its effect on protein expression and regulation mechanisms during neural differentiation.Treatment with venlafaxine decreased expression of prolyl 4-hydroxylase (P4HB), ubiquitin-conjugating enzyme E2K (HIP2) and plastin 3 (T-plastin), and up-regulated expression of growth factor beta-3 (TGF-β3), dihydropyrimidinase-like 3 (DPYSL3), and pyruvate kinase (PKM) after differentiation for 1 and 7 days.Our findings may contribute to improve understanding of molecular mechanism of venlafaxine.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Life Sciences, Hanyang University, Ansan, Republic of Korea.

ABSTRACT

Objective: Antidepressants are known to positively influence several factors in patients with depressive disorders, resulting in increased neurogenesis and subsequent relief of depressive disorders. To study the effects of venlafaxine during neural differentiation at the cellular level, we looked at its effect on protein expression and regulation mechanisms during neural differentiation.

Methods: After exposing NCCIT cell-derived EBs to venlafaxine during differentiation (1 day and 7 days), changes in protein expression were analyzed by 2-DE and MALDI-TOF MS analysis. Gene levels of proteins regulated by venlafaxine were analyzed by real-time RT-PCR.

Results: Treatment with venlafaxine decreased expression of prolyl 4-hydroxylase (P4HB), ubiquitin-conjugating enzyme E2K (HIP2) and plastin 3 (T-plastin), and up-regulated expression of growth factor beta-3 (TGF-β3), dihydropyrimidinase-like 3 (DPYSL3), and pyruvate kinase (PKM) after differentiation for 1 and 7 days. In cells exposed to venlafaxine, the mRNA expression patterns of HIP2 and PKM, which function as negative and positive regulators of differentiation and neuronal survival, respectively, were consistent with the observed changes in protein expression.

Conclusion: Our findings may contribute to improve understanding of molecular mechanism of venlafaxine.

No MeSH data available.


Related in: MedlinePlus