Role of Calpain and Its Inhibitors in Tissue Degeneration and Neuroprotection in Spinal Cord Injury<sup>a</sup>

Banik, Naren L.; Matzelle, Denise; Gantt-Wilford, Gloria; Hogan, Edward L.

doi:10.1111/j.1749-6632.1997.tb48421.x

Cited by 17 publications

(12 citation statements)

References 29 publications

(37 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Proteolytic targets of calpain include cytoskeletal proteins such as neurofilament, spectrin, and membrane proteins such as growth factor receptors [62,63], cytokines [64,65] and transcription factors [66]. In the current study, long-term GMCSF or GCSF exposure led to robust transcriptional increase in the expression of calpain 2 and 7, but not other calpain family members, in sensory neurons.…”

Section: Discussionmentioning

confidence: 63%

Transcriptional Mechanisms Underlying Sensitization of Peripheral Sensory Neurons by Granulocyte-/Granulocyte-Macrophage Colony Stimulating Factors

et al. 2013

View full text Add to dashboard Cite

BackgroundCancer-associated pain is a major cause of poor quality of life in cancer patients and is frequently resistant to conventional therapy. Recent studies indicate that some hematopoietic growth factors, namely granulocyte macrophage colony stimulating factor (GMCSF) and granulocyte colony stimulating factor (GCSF), are abundantly released in the tumor microenvironment and play a key role in regulating tumor-nerve interactions and tumor-associated pain by activating receptors on dorsal root ganglion (DRG) neurons. Moreover, these hematopoietic factors have been highly implicated in postsurgical pain, inflammatory pain and osteoarthritic pain. However, the molecular mechanisms via which G-/GMCSF bring about nociceptive sensitization and elicit pain are not known.ResultsIn order to elucidate G-/GMCSF mediated transcriptional changes in the sensory neurons, we performed a comprehensive, genome-wide analysis of changes in the transcriptome of DRG neurons brought about by exposure to GMCSF or GCSF. We present complete information on regulated genes and validated profiling analyses and report novel regulatory networks and interaction maps revealed by detailed bioinformatics analyses. Amongst these, we validate calpain 2, matrix metalloproteinase 9 (MMP9) and a RhoGTPase Rac1 as well as Tumor necrosis factor alpha (TNFα) as transcriptional targets of G-/GMCSF and demonstrate the importance of MMP9 and Rac1 in GMCSF-induced nociceptor sensitization.ConclusionWith integrative approach of bioinformatics, in vivo pharmacology and behavioral analyses, our results not only indicate that transcriptional control by G-/GMCSF signaling regulates a variety of established pain modulators, but also uncover a large number of novel targets, paving the way for translational analyses in the context of pain disorders.

show abstract

Section: Discussionmentioning

confidence: 63%

Transcriptional Mechanisms Underlying Sensitization of Peripheral Sensory Neurons by Granulocyte-/Granulocyte-Macrophage Colony Stimulating Factors

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Spinal cord trauma leads to increased expression of death receptors and their ligands as well as activation of caspases and calpain (19,23,36). Previous studies have shown that SCI triggers apoptotic cell death of oligodendrocytes associated with white matter tracts within 3 to 4 days after injury (20).…”

Section: Discussionmentioning

confidence: 99%

Umbilical Cord Blood Stem Cell Mediated Downregulation of Fas Improves Functional Recovery of Rats after Spinal Cord Injury

Dasari

Spomar

et al. 2007

Neurochem Res

View full text Add to dashboard Cite

Human umbilical cord blood stem cells (hUCB), due to their primitive nature and ability to develop into nonhematopoietic cells of various tissue lineages, represent a potentially useful source for cellbased therapies after spinal cord injury (SCI). To evaluate their therapeutic potential, hUCB were stereotactically transplanted into the injury epicenter, one week after SCI in rats. Our results show the presence of a substantial number of surviving hUCB in the injured spinal cord up to five weeks after transplantation. Three weeks after SCI, apoptotic cells were found especially in the dorsal white matter and gray matter, which are positive for both neuron and oligodendrocyte markers. Expression of Fas on both neurons and oligodendrocytes was efficiently downregulated by hUCB. This ultimately resulted in downregulation of caspase-3 extrinsic pathway proteins involving increased expression of FLIP, XIAP and inhibition of PARP cleavage. In hUCB-treated rats, the PI3K/Akt pathway was also involved in antiapoptotic actions. Further, structural integrity of the cytoskeletal proteins α-tubulin, MAP2A&2B and NF-200 has been preserved in hUCB treatments. The behavioral scores of hind limbs of hUCB-treated rats improved significantly than those of the injured group, showing functional recovery. Taken together, our results indicate that hUCB-mediated downregulation of Fas and caspases leads to functional recovery of hind limbs of rats after SCI.

show abstract

“…After SCI, some cellular demise was directly related to post-traumatic necrosis, whereas others die due to apoptosis (Crowe et al, 1997;Emery et al, 1998;Shuman et al, 1997;Springer et al, 1999;Keane et al, 2001;Warden et al, 2001;Beattie et al, 2002). Spinal cord trauma activates upregulation of caspases and calpain and the apoptotic machinery, leading to increased expression of death receptors and their ligands (Banik et al, 1997;Casha et al, 2001;Keane et al, 2001;Springer et al, 1999). However, there are conflicting reports as to the role of cell death in SCI-probably a reflection of the known dual capacity of TNF to be both pro-and anti-apoptotic.…”

Section: Apoptosis After Scimentioning

confidence: 99%

Mesenchymal Stem Cell Therapy for Apoptosis After Spinal Cord Injury

Dasari¹,

Veeravalli²,

Rao³

et al. 2011

Advanced Understanding of Neurodegenerative Diseases

View full text Add to dashboard Cite

Role of Calpain and Its Inhibitors in Tissue Degeneration and Neuroprotection in Spinal Cord Injury^a

Cited by 17 publications

References 29 publications

Transcriptional Mechanisms Underlying Sensitization of Peripheral Sensory Neurons by Granulocyte-/Granulocyte-Macrophage Colony Stimulating Factors

Transcriptional Mechanisms Underlying Sensitization of Peripheral Sensory Neurons by Granulocyte-/Granulocyte-Macrophage Colony Stimulating Factors

Umbilical Cord Blood Stem Cell Mediated Downregulation of Fas Improves Functional Recovery of Rats after Spinal Cord Injury

Mesenchymal Stem Cell Therapy for Apoptosis After Spinal Cord Injury

Contact Info

Product

Resources

About

Role of Calpain and Its Inhibitors in Tissue Degeneration and Neuroprotection in Spinal Cord Injurya

Cited by 17 publications

References 29 publications

Transcriptional Mechanisms Underlying Sensitization of Peripheral Sensory Neurons by Granulocyte-/Granulocyte-Macrophage Colony Stimulating Factors

Transcriptional Mechanisms Underlying Sensitization of Peripheral Sensory Neurons by Granulocyte-/Granulocyte-Macrophage Colony Stimulating Factors

Umbilical Cord Blood Stem Cell Mediated Downregulation of Fas Improves Functional Recovery of Rats after Spinal Cord Injury

Mesenchymal Stem Cell Therapy for Apoptosis After Spinal Cord Injury

Contact Info

Product

Resources

About

Role of Calpain and Its Inhibitors in Tissue Degeneration and Neuroprotection in Spinal Cord Injury^a