Antibody to caspase-cleaved actin detects apoptosis in differentiated neuroblastoma and plaque-associated neurons and microglia in Alzheimer's disease

Fusheng Yang, Xiaoyan Sun, Walter Beech, Bruce Teter, Sherry Wu, Jason Sigel, Harry V. Vinters, Sally A. Frautschy, Greg M. Cole

Research output: Contribution to journalArticle

220 Citations (Scopus)

Abstract

During apoptosis, activation of a family of cysteine proteases related to interleukin-1β-converting enzyme (ICE)-related proteases or 'caspases' results in endoproteolytic cleavage of multiple substrates at specific aspartate residues. We have sought to develop new antibody probes for the neoepitopes in protein fragments produced by ICE-related proteolytic cleavage as specific markers of events tightly linked to apoptotic mechanisms. Here, we demonstrate that an antibody probe specific for the C terminus of a 32-kd actin fragment produced by ICE-like activity specifically labels apoptotic but not necrotic, differentiated human neuroblastoma cells in culture. Unlike probes for nonspecific DNA strand breaks confined to the nucleus or cell body, this method allows the detection of cytoskeletal fragments in cell processes as well as the perikaryon long before DNA fragmentation and cell death and therefore serves as a novel marker of apoptosis-related events in distal parts of cells such as axons and dendrites. To illustrate this new tool, we show that the antibody detects the processes and cell bodies of degenerating neurons and plaque-associated microglia in Alzheimer's disease. In situ detection of caspase-cleaved actin provides a new means to evaluate the role of caspase activation in pathological and physiological processes.

Original languageEnglish (US)
Pages (from-to)379-389
Number of pages11
JournalAmerican Journal of Pathology
Volume152
Issue number2
StatePublished - Feb 1998
Externally publishedYes

Fingerprint

Caspase 1
Microglia
Caspases
Neuroblastoma
Actins
Alzheimer Disease
Apoptosis
Neurons
Antibodies
Physiological Phenomena
DNA Breaks
Cysteine Proteases
DNA Fragmentation
Pathologic Processes
Dendrites
Aspartic Acid
Axons
Peptide Hydrolases
Cell Death
Cell Culture Techniques

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Antibody to caspase-cleaved actin detects apoptosis in differentiated neuroblastoma and plaque-associated neurons and microglia in Alzheimer's disease. / Yang, Fusheng; Sun, Xiaoyan; Beech, Walter; Teter, Bruce; Wu, Sherry; Sigel, Jason; Vinters, Harry V.; Frautschy, Sally A.; Cole, Greg M.

In: American Journal of Pathology, Vol. 152, No. 2, 02.1998, p. 379-389.

Research output: Contribution to journalArticle

Yang, F, Sun, X, Beech, W, Teter, B, Wu, S, Sigel, J, Vinters, HV, Frautschy, SA & Cole, GM 1998, 'Antibody to caspase-cleaved actin detects apoptosis in differentiated neuroblastoma and plaque-associated neurons and microglia in Alzheimer's disease', American Journal of Pathology, vol. 152, no. 2, pp. 379-389.
Yang, Fusheng ; Sun, Xiaoyan ; Beech, Walter ; Teter, Bruce ; Wu, Sherry ; Sigel, Jason ; Vinters, Harry V. ; Frautschy, Sally A. ; Cole, Greg M. / Antibody to caspase-cleaved actin detects apoptosis in differentiated neuroblastoma and plaque-associated neurons and microglia in Alzheimer's disease. In: American Journal of Pathology. 1998 ; Vol. 152, No. 2. pp. 379-389.
@article{897ec6fe889a4bb48e063b54127ee087,
title = "Antibody to caspase-cleaved actin detects apoptosis in differentiated neuroblastoma and plaque-associated neurons and microglia in Alzheimer's disease",
abstract = "During apoptosis, activation of a family of cysteine proteases related to interleukin-1β-converting enzyme (ICE)-related proteases or 'caspases' results in endoproteolytic cleavage of multiple substrates at specific aspartate residues. We have sought to develop new antibody probes for the neoepitopes in protein fragments produced by ICE-related proteolytic cleavage as specific markers of events tightly linked to apoptotic mechanisms. Here, we demonstrate that an antibody probe specific for the C terminus of a 32-kd actin fragment produced by ICE-like activity specifically labels apoptotic but not necrotic, differentiated human neuroblastoma cells in culture. Unlike probes for nonspecific DNA strand breaks confined to the nucleus or cell body, this method allows the detection of cytoskeletal fragments in cell processes as well as the perikaryon long before DNA fragmentation and cell death and therefore serves as a novel marker of apoptosis-related events in distal parts of cells such as axons and dendrites. To illustrate this new tool, we show that the antibody detects the processes and cell bodies of degenerating neurons and plaque-associated microglia in Alzheimer's disease. In situ detection of caspase-cleaved actin provides a new means to evaluate the role of caspase activation in pathological and physiological processes.",
author = "Fusheng Yang and Xiaoyan Sun and Walter Beech and Bruce Teter and Sherry Wu and Jason Sigel and Vinters, {Harry V.} and Frautschy, {Sally A.} and Cole, {Greg M.}",
year = "1998",
month = "2",
language = "English (US)",
volume = "152",
pages = "379--389",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - Antibody to caspase-cleaved actin detects apoptosis in differentiated neuroblastoma and plaque-associated neurons and microglia in Alzheimer's disease

AU - Yang, Fusheng

AU - Sun, Xiaoyan

AU - Beech, Walter

AU - Teter, Bruce

AU - Wu, Sherry

AU - Sigel, Jason

AU - Vinters, Harry V.

AU - Frautschy, Sally A.

AU - Cole, Greg M.

PY - 1998/2

Y1 - 1998/2

N2 - During apoptosis, activation of a family of cysteine proteases related to interleukin-1β-converting enzyme (ICE)-related proteases or 'caspases' results in endoproteolytic cleavage of multiple substrates at specific aspartate residues. We have sought to develop new antibody probes for the neoepitopes in protein fragments produced by ICE-related proteolytic cleavage as specific markers of events tightly linked to apoptotic mechanisms. Here, we demonstrate that an antibody probe specific for the C terminus of a 32-kd actin fragment produced by ICE-like activity specifically labels apoptotic but not necrotic, differentiated human neuroblastoma cells in culture. Unlike probes for nonspecific DNA strand breaks confined to the nucleus or cell body, this method allows the detection of cytoskeletal fragments in cell processes as well as the perikaryon long before DNA fragmentation and cell death and therefore serves as a novel marker of apoptosis-related events in distal parts of cells such as axons and dendrites. To illustrate this new tool, we show that the antibody detects the processes and cell bodies of degenerating neurons and plaque-associated microglia in Alzheimer's disease. In situ detection of caspase-cleaved actin provides a new means to evaluate the role of caspase activation in pathological and physiological processes.

AB - During apoptosis, activation of a family of cysteine proteases related to interleukin-1β-converting enzyme (ICE)-related proteases or 'caspases' results in endoproteolytic cleavage of multiple substrates at specific aspartate residues. We have sought to develop new antibody probes for the neoepitopes in protein fragments produced by ICE-related proteolytic cleavage as specific markers of events tightly linked to apoptotic mechanisms. Here, we demonstrate that an antibody probe specific for the C terminus of a 32-kd actin fragment produced by ICE-like activity specifically labels apoptotic but not necrotic, differentiated human neuroblastoma cells in culture. Unlike probes for nonspecific DNA strand breaks confined to the nucleus or cell body, this method allows the detection of cytoskeletal fragments in cell processes as well as the perikaryon long before DNA fragmentation and cell death and therefore serves as a novel marker of apoptosis-related events in distal parts of cells such as axons and dendrites. To illustrate this new tool, we show that the antibody detects the processes and cell bodies of degenerating neurons and plaque-associated microglia in Alzheimer's disease. In situ detection of caspase-cleaved actin provides a new means to evaluate the role of caspase activation in pathological and physiological processes.

UR - http://www.scopus.com/inward/record.url?scp=0031930313&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031930313&partnerID=8YFLogxK

M3 - Article

C2 - 9466564

AN - SCOPUS:0031930313

VL - 152

SP - 379

EP - 389

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 2

ER -