Proteomic Analysis of Cerebrospinal Fluid in Canine Cervical Spondylomyelopathy

Martín-Vaquero, Paula; Costa, Ronaldo C. da; Allen, Matthew J.; Moore, Sarah A.; Keirsey, Jeremy; Green, Kari B.

doi:10.1097/brs.0000000000000831

Cited by 19 publications

(40 citation statements)

References 102 publications

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“…Proteomics and bioinformatics. Proteomics analysis was performed by the OSU Proteomics Core, as previously described (25). Briefly, samples were marked with dye and subjected to two-dimensional electrophoretic separation (Fig.…”

Section: Methodsmentioning

confidence: 99%

Increased hypoxia-inducible factor-1α in striated muscle of tumor-bearing mice

Devine

Bicer

Reiser

et al. 2017

American Journal of Physiology-Heart and Circulatory Physiology

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Cancer cachexia is a progressive wasting disease resulting in significant effects on the quality of life and high mortality. Most studies on cancer cachexia have focused on skeletal muscle; however, the heart is now recognized as a major site of cachexia-related effects. To elucidate possible mechanisms, a proteomic study was performed on the left ventricles of colon-26 (C26) adenocarcinoma tumor-bearing mice. The results revealed several changes in proteins involved in metabolism. An integrated pathway analysis of the results revealed a common mediator in hypoxia-inducible factor-1α (HIF-1α). Work by other laboratories has shown that extensive metabolic restructuring in the C26 mouse model causes changes in gene expression that may be affected directly by HIF-1α, such as glucose metabolic genes. M-mode echocardiography showed progressive decline in heart function by , exhibited by significantly decreased ejection fraction and fractional shortening, along with posterior wall thickness. Using Western blot analysis, we confirmed that HIF-1α is significantly upregulated in the heart, whereas there were no changes in its regulatory proteins, prolyl hydroxylase domain-containing protein 2 (PHD2) and von Hippel-Lindau protein (VHL). PHD2 requires both oxygen and iron as cofactors for the hydroxylation of HIF-1α, marking it for ubiquination via VHL and subsequent destruction by the proteasome complex. We examined venous blood gas values in the tumor-bearing mice and found significantly lower oxygen concentration compared with control animals in the third week after tumor inoculation. We also examined select skeletal muscles to determine whether they are similarly affected. In the diaphragm, extensor digitorum longus, and soleus, we found significantly increased HIF-1α in tumor-bearing mice, indicating a hypoxic response, not only in the heart, but also in skeletal muscle. These results indicate that HIF-1α may contribute, in part, to the metabolic changes that occur during cancer cachexia. We used proteomics and metadata analysis software to identify contributors to metabolic changes in striated muscle during cancer cachexia. We found increased expression of hypoxia-inducible factor-1α in the heart and skeletal muscle, suggesting a potential target for the therapeutic treatment of cancer cachexia.

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Section: Methodsmentioning

confidence: 99%

Increased hypoxia-inducible factor-1α in striated muscle of tumor-bearing mice

Devine

Bicer

Reiser

et al. 2017

American Journal of Physiology-Heart and Circulatory Physiology

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“…Protein was extracted from transmural myocardial biopsies from perfused and ischemia-reperfusion regions, prepared for capillary-LC-nanospray-MS/MS and subsequent label free quantitation. Proteomic quantifications were performed in accordance with previous studies [42, 53] In brief mass spectrometry methodology that is detailed in the online supplement. In brief, protein quantification and identification was accomplished using the NCBInr Other Mammalia Database (version 20150104, 1,412,788 sequences).…”

Section: Methodsmentioning

confidence: 99%

Obesity alters molecular and functional cardiac responses to ischemia/reperfusion and glucagon-like peptide-1 receptor agonism

et al. 2016

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This study tested the hypothesis that obesity alters the cardiac response to ischemia/reperfusion and/or glucagon like peptide-1 (GLP-1) receptor activation, and that these differences are associated with alterations in the obese cardiac proteome and microRNA (miR) transcriptome. Ossabaw swine were fed normal chow or obesogenic diet for 6 months. Cardiac function was assessed at baseline, during a 30-min coronary occlusion, and during 2 hours of reperfusion in anesthetized swine treated with saline or exendin-4 for 24 hours. Cardiac biopsies were obtained from normal and ischemia/reperfusion territories. Fat-fed animals were heavier, and exhibited hyperinsulinemia, hyperglycemia, and hypertriglyceridemia. Plasma troponin-I concentration (index of myocardial injury) was increased following ischemia/reperfusion and decreased by exendin-4 treatment in both groups. Ischemia/reperfusion produced reductions in systolic pressure and stroke volume in lean swine. These indices were higher in obese hearts at baseline and relatively maintained throughout ischemia/reperfusion. Exendin-4 administration increased systolic pressure in lean swine but did not affect blood pressure in obese swine. End-diastolic volume was reduced by exendin-4 following ischemia/reperfusion in obese swine. These divergent physiologic responses were associated with obesity-related differences in proteins related to myocardial structure/function (e.g. titin) and calcium handling (e.g. SERCA2a, histidine-rich Ca2+ binding protein). Alterations in expression of cardiac miRs in obese hearts included miR-15, miR-27, miR-130, miR-181, and let-7. Taken together, these observations validate this discovery approach and reveal novel associations that suggest previously undiscovered mechanisms contributing to the effects of obesity on the heart and contributing to the actions of GLP-1 following ischemia/reperfusion.

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“…Supportively, VB 12 deficiency was observed to lead to degenerative diseases development of the nervous system and might be correlated with CSM incidence . It was also found that differentially expressed proteins were partially responsible for bone turnover, damaged neural tissue, and/or compromised blood‐spinal cord barrier . Vitamin D insufficiency significantly impaired implant osseointegration in a rat model .…”

Section: Discussionmentioning

confidence: 89%

“…28 It was also found that differentially expressed proteins were partially responsible for bone turnover, damaged neural tissue, and/or compromised blood-spinal cord barrier. 29 Vitamin D insufficiency significantly impaired implant osseointegration in a rat model. 30 These findings indicate that 25(OH)D has the potential to predict prognosis of CSM.…”

Section: Postoperative Plasma Vdbp 25(oh)d and Gsh Levels Are Incmentioning

confidence: 99%

Plasma VDBP, 25(OH)D, and GSH levels predict surgical outcome in patients with cervical spondylotic myelopathy

Peng

Zhan

Liu

et al. 2019

The Kaohsiung J of Med Scie

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This study intends to investigate the predictive values of plasma Vitamin D‐binding protein (VDBP), 25‐hydroxyvitamin D [25(OH)D], and glutathione (GSH) levels in the outcome of cervical spondylotic myelopathy (CSM) surgery. Surgery outcomes of 236 CSM patients were determined. Recovery rate was calculated according to Japanese Orthopaedic Association (JOA) scores during follow‐up. CSM patients with a recovery rate >50% were assigned with good prognosis and the rest were with fair prognosis. Preoperative and postoperative neurologic function scores were compared among groups. Plasma VDBP and 25(OH)D levels, as well as GSH levels were measured by ELISA and glutathione reductase recycling assay, respectively. Pearson's correlation coefficient was performed to analyze the correlation among plasma VDBP, 25(OH)D, and GSH levels. Receiver operating characteristic (ROC) curve was applied to evaluate the predictive value of plasma VDBP, 25(OH)D, and GSH levels for surgical outcome. Logistic regression model was used to analyze risk factors for surgical outcome. Compared with those with fair prognosis, CSM patients with good prognosis group exhibited higher postoperative neurologic function scores, plasma VDBP, 25(OH)D, and GSH levels, and better improvements in spinal cord compression and motions of the cervical vertebra. Plasma VDBP, 25(OH)D, and GSH levels were favorable prognostic factors for CSM surgical outcome. The sensitivity and specificity of plasma VDBP, plasma 25(OH)D, and plasma GSH were 89.8% and 91.7%, 85.8% and 84.4%, and 79.5% and 91.7%, respectively. Our study provides evidence that higher plasma VDBP, 25(OH)D, and GSH levels may predict better surgical outcome in CSM patients.

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Proteomic Analysis of Cerebrospinal Fluid in Canine Cervical Spondylomyelopathy

Cited by 19 publications

References 102 publications

Increased hypoxia-inducible factor-1α in striated muscle of tumor-bearing mice

Increased hypoxia-inducible factor-1α in striated muscle of tumor-bearing mice

Obesity alters molecular and functional cardiac responses to ischemia/reperfusion and glucagon-like peptide-1 receptor agonism

Plasma VDBP, 25(OH)D, and GSH levels predict surgical outcome in patients with cervical spondylotic myelopathy

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