Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Lamin A, An Activator of Longevity/Anti-Aging SIRT1 Protein

a technology of longevity and anti-aging sirt1 protein, which is applied in the field of lamin a, an activator of longevity/anti-aging sirt1 protein, can solve the problem of unclear underlying mechanism, and achieve the effects of increasing the activity of deacetylase sirt1, reducing and increasing the binding affinity of lamin a

Inactive Publication Date: 2014-05-15
THE UNIVERSITY OF HONG KONG
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent describes a method for reducing the activity of a protein called SIRT1 using an inhibitor of another protein called lamin A. This invention can be useful for researchers studying the function of SIRT1 and for treating diseases related to excessive activity of this enzyme.

Problems solved by technology

Therefore, despite various beneficial effects of resveratrol and mimics, the underlying mechanism is still unclear.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Lamin A, An Activator of Longevity/Anti-Aging SIRT1 Protein
  • Lamin A, An Activator of Longevity/Anti-Aging SIRT1 Protein
  • Lamin A, An Activator of Longevity/Anti-Aging SIRT1 Protein

Examples

Experimental program
Comparison scheme
Effect test

example 1

SIRT1 Interacts with Lamin A While Prelamin A or Progerin Jeopardizes the Interaction

[0116]To determine the potential involvement of SIRT1 in progeria, the potential interaction between lamin A and SIRT1 is examined by co-immunoprecipitation in HEK293 cells expressing ectopic FLAG-tagged SIRT1.

[0117]Lamin A was pulled down in the anti-FLAG immunoprecipitates, while FLAG-SIRT1 was detected in the anti-lamin A / C immunoprecipitates (FIG. 1A). The interaction between endogenous SIRT1 and lamin A / C was confirmed in HEK293 cells, bone marrow stromal cells (BMSCs), and mouse embryonic fibroblasts (MEFs), where anti-SIRT1 immunoprecipitates pulled down lamin A and vice versa (FIGS. 1B, 6A, 6B).

[0118]Immunofluorescence confocal microscopy showed that much of nuclear SIRT1 co-localized with nucleoplasmic lamin A / C in the nuclear interior in human fibroblasts (FIG. 1C). Consistently, ectopic EGFP-SIRT1 and DsRed-lamin A co-existed in the nuclear interior (FIG. 1D). This interaction seems spec...

example 2

SIRT1 is Mislocalized in Progeria Cells

[0123]Lamin A is one of the major components of NM. This Example investigates the association of SIRT1 with the NM by subcellular fractionation. SIRT1− / − cells were utilized as a negative control for the specific staining of SIRT1 protein. KAP-1 (KRAB-associated protein 1, also known as Trim28 or Tif1β) and MCM3 proteins served as positive controls for the purity of the subcellular fractionation.

[0124]KAP-1 is a heterochromatin factor and was reported to be associated with the majority of the micrococcal nuclease-resistant fraction in the nucleus (Goodarzi et al., 2008; Ryan et al., 1999). MCM3 protein is important in preventing excessive DNA replication during S phase and is predominantly associated with chromatin (Mendez and Stillman, 2000).

[0125]As expected, Kap-1 was resistant to MNase digestion and remained in the NM fraction (P2′) whereas the majority of Mcm3 was released into the nucleoplasmic and chromatic fraction (S2′) after MNase tre...

example 3

Resveratrol Enhances the Binding of SIRT1 to Lamin A and Stimulates its Deacetylase Activity in a Lamin A-Dependent Manner

[0132]The NM-localization of SIRT1 and the association of NM with HDAC deacetylase activity (Fey et al., 1991) suggest that NM might contain potential SIRT1 activators. To test this hypothesis, in vitro deacetylase activity of rhSIRT1 by a BioMol® SIRT1 Fluorimetric Drug Discovery Kit (BSDK) was quantified in the presence or absence of NM derived from wild-type or Zmpste24− / − BMSCs.

[0133]Surprisingly, the deacetylase activity of rhSIRT1 was enhanced approximately 3-fold in the presence of NM from wild-type BMSCs compared with the control without NM or with cytoplasmic fraction (FIG. 7E), suggesting the existence of potential SIRT1 activator(s) on the NM. In contrast, the NM from the Zmpste24− / − BMSCs showed a significantly reduced stimulatory effect on rhSIRT1 deacetylase activity.

[0134]This Example further investigates whether lamin A acts as an activator of SI...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
molar ratioaaaaaaaaaa
molar ratioaaaaaaaaaa
molar ratioaaaaaaaaaa
Login to View More

Abstract

In one embodiment, the present invention provides methods of modulating the deacetylase activity of SIRT1 in one or more cell by modifying the binding affinity of lamin A to SIRT1 via one or more interaction modifying compound. In another embodiment, the present invention provides methods of screening SIRT1-activating / inhibiting compounds based on the interaction between lamin A and SIRT1 proteins and SIRT1-activating property of lamin A. In another embodiment, the present invention provides uses of SIRT1-activating compounds to treat patient(s) suffering from metabolic and / or aging-related degenerative diseases, and uses of SIRT1-inhibiting compounds to treat human malignancies.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]This application claims the benefit of U.S. provisional application Ser. No. 61 / 725,252, filed Nov. 12, 2012, which is herein incorporated by reference in its entirety.BACKGROUND OF THE INVENTION[0002]Sirtuins (silent mating type information regulation 2 homolog), class III HDACs containing NAD+-dependent protein deacetylase and ADP-ribosyltransferase activities, regulate various metabolic pathways (Denu, 2005; Donmez and Guarente, 2010; Finkel et al., 2009; Haigis and Sinclair, 2010).[0003]Of seven mammalian sirtuins, SIRT1 (NAD-dependent deacetylase sirtuin-1) is the closest homolog of Saccharomyces cerevesiae Sir2 (silent information regulator 2) identified three decades ago (Klar et al., 1979). Loss of SIRT1 causes defective gametogenesis, heart and retinal abnormalities, genomic instability, small body size, and reduced survival in mice (Cheng et al., 2003; McBurney et al., 2003; Wang et al., 2008); and abolishes many beneficial effec...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/16C12Q1/37
CPCC12Q1/37A61K38/16A61K31/05A61K38/1709A61P3/00A61P35/00A61P39/00C12Q1/34G01N2333/98G01N2500/02G01N2500/04G01N33/573G01N2333/47G01N2333/91142G01N2500/10
Inventor ZHOU, ZHONGJUNLIU, BAOHUA
Owner THE UNIVERSITY OF HONG KONG
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com