A composition for regulation cellular senescence comprising lysophosphatidic acid and inhibitor of adenylyl cyclase as active ingredients

A technology of adenylate cyclase and lysophosphatidic acid, which can be applied in the directions of active ingredients of heterocyclic compounds, medical preparations containing active ingredients, and drug combinations, etc., can solve the problems of decreased phosphorylation of Thr-172 and the like

Inactive Publication Date: 2011-04-20
SEOUL NAT UNIV R&DB FOUND
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Phosphorylation of Ser485 / 491 by PKA or PKB / AKT inhibits the α-Thr-172 pathway, leading to a decrease in Thr-172 phosphorylation

Method used

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  • A composition for regulation cellular senescence comprising lysophosphatidic acid and inhibitor of adenylyl cyclase as active ingredients
  • A composition for regulation cellular senescence comprising lysophosphatidic acid and inhibitor of adenylyl cyclase as active ingredients
  • A composition for regulation cellular senescence comprising lysophosphatidic acid and inhibitor of adenylyl cyclase as active ingredients

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Experimental program
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Embodiment

[0054] 1. Materials

[0055] Dulbecco's modified Eagle's medium (DMEM: JBI) was used as the medium for cell culture here, and LPA, propidium iodide (PI) and trypan blue were purchased from Sigma (St. Louis, Missouri, USA). . 10% fetal bovine serum (FBS), penicillin and streptomycin (antibiotics for cell culture) were purchased from Gibco / BRL (Carlsbad, CA, USA). Polyclonal antibodies against AMPKα, p-Thr172-AMPKα, p-Ser485 / 491-AMPKα, p53, p-Ser15-p53 and p21WAF1 / CIP1 were purchased from Cell Signaling (Beverly, MA, USA). Polyclonal antibody against β-actin was purchased from Santa Cruz (California, USA). The PKA inhibitor Rp-cAMP and the AC inhibitor ACI (SQ22536) were purchased from CalBiochem (San Diego, CA, USA). Horseradish peroxidase-conjugated anti-rabbit IgG and anti-mouse IgG were purchased as secondary antibodies from Zymed (South San Francisco, CA, USA). NC membranes (nitrocellulose membranes) for immunoblotting were purchased from Schleicher & Schuell (Dassel, G...

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Abstract

The present invention relates to the molecular mechanism inducing cell proliferation in aged human fibroblasts by inhibiting AMPK using LPA and AC inhibitor. Particularly, the present invention relates to a composition comprising LPA and ACI as active ingredients and the invention proves with the said composition that LPA and ACI regulate different phosphorylation of AMPK a and thus inactivate p53 and induce senescent cell proliferation. This results support the fact that AMPK signal transduction plays an important role in cell proliferation of senescent cells.

Description

technical field [0001] The present invention relates to a composition containing adenylate cyclase (ACI) and lysophosphatidic acid (LPA) as active ingredients for regulating cell aging, more specifically, the present invention relates to a composition containing LPA and ACI as active ingredients A composition for regulating cell senescence and a method for regulating cell senescence, the method includes the step of treating senescent cells with an effective dose of the composition. Background technique [0002] Cellular senescence plays an important role in complex biological processes including development, maturation, and tumorigenesis. Accordingly, numerous attempts have been made to understand fundamental and important properties in cellular senescence (Peacocke and Campisi, 1991; Smith and Pereira-Smith, 1996). One of the hallmarks of cellular senescence is hyporesponsiveness to growth factors and mitogens. [0003] Lysophosphatidic acid (LPA) is an important mitogen ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/52A61K8/64C12Q1/00
CPCA61K8/606A61Q19/08A61K8/553A61K8/49A61K8/4906A61K31/52A61K2800/782A61P43/00
Inventor 朴相哲吕义珠林志宪
Owner SEOUL NAT UNIV R&DB FOUND
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