Proteomic profile of Citrus grandis roots under long-term boron-deficiency revealed by iTRAQ

Mercury is a severe environmental pollutant with neurotoxic effects, especially when exposed for long periods. Although there are several evidences regarding mercury toxicity, little is known about inorganic mercury (IHg) species and cerebellum, one of the main targets of mercury associated with the neurological symptomatology of mercurial poisoning. Besides that, the global proteomic profile assessment is a valuable tool to screen possible biomarkers and elucidate molecular targets of mercury neurotoxicity; however, the literature is still scarce. Thus, this study aimed to investigate the effects of long-term exposure to IHg in adult rats’ cerebellum and explore the modulation of the cerebellar proteome associated with biochemical and functional outcomes, providing evidence, in a translational perspective, of new mercury toxicity targets and possible biomarkers. Fifty-four adult rats were exposed to 0.375 mg/kg of HgCl2 or distilled water for 45 days using intragastric gavage. Then, the motor functions were evaluated by rotarod and inclined plane. The cerebellum was collected to quantify mercury levels, to assess the antioxidant activity against peroxyl radicals (ACAPs), the lipid peroxidation (LPO), the proteomic profile, the cell death nature by cytotoxicity and apoptosis, and the Purkinje cells density. The IHg exposure increased mercury levels in the cerebellum, reducing ACAP and increasing LPO. The proteomic approach revealed a total 419 proteins with different statuses of regulation, associated with different biological processes, such as synaptic signaling, energy metabolism and nervous system development, e.g., all these molecular changes are associated with increased cytotoxicity and apoptosis, with a neurodegenerative pattern on Purkinje cells layer and poor motor coordination and balance. In conclusion, all these findings feature a neurodegenerative process triggered by IHg in the cerebellum that culminated into motor functions deficits, which are associated with several molecular features and may be related to the clinical outcomes of people exposed to the toxicant.

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Long-Term Lead Exposure Since Adolescence Causes Proteomic and Morphological Alterations in the Cerebellum Associated with Motor Deficits in Adult Rats

International Journal of Molecular Sciences ◽

10.3390/ijms21103571 ◽

2020 ◽

Vol 21 (10) ◽

pp. 3571 ◽

Cited By ~ 4

Author(s):

Luana Ketlen Reis Leão ◽

Leonardo Oliveira Bittencourt ◽

Ana Carolina Oliveira ◽

Priscila Cunha Nascimento ◽

Giza Hellen Nonato Miranda ◽

...

Keyword(s):

Synaptic Vesicles ◽

Motor Performance ◽

Second Messengers ◽

Motor Deficits ◽

Proteomic Profile ◽

Adult Rats ◽

Morphological Alterations ◽

Male Wistar Rats ◽

Mature Neurons

Lead (Pb) is an environmental contaminant that presents a high risk for human health. We aimed to investigate the possible alterations triggered by the exposure to Pb acetate for a long period in motor performance and the possible relationship with biochemical, proteomic and morphological alterations in the cerebellum of rats. Male Wistar rats were exposed for 55 days, at 50 mg/Kg of Pb acetate, and the control animals received distilled water. Open field (OF) and rotarod tests; biochemistry parameters (MDA and nitrite); staining/immunostaining of Purkinje cells (PC), mature neurons (MN), myelin sheath (MS) and synaptic vesicles (SYN) and proteomic profile were analyzed. Pb deposition on the cerebellum area and this study drove to exploratory and locomotion deficits and a decrease in the number of PC, MN, SYN and MS staining/immunostaining. The levels of MDA and nitrite remained unchanged. The proteomic profile showed alterations in proteins responsible for neurotransmitters release, as well as receptor function and second messengers signaling, and also proteins involved in the process of apoptosis. Thus, we conclude that the long-term exposure to low Pb dose promoted locomotion and histological tracings, associated with alterations in the process of cell signaling, as well as death by apoptosis.

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Lead-Induced Motor Dysfunction Is Associated with Oxidative Stress, Proteome Modulation, and Neurodegeneration in Motor Cortex of Rats

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/5595047 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Luana Ketlen Reis Leão ◽

Leonardo Oliveira Bittencourt ◽

Ana Carolina Alves Oliveira ◽

Priscila Cunha Nascimento ◽

Maria Karolina Martins Ferreira ◽

...

Keyword(s):

Oxidative Stress ◽

Motor Cortex ◽

Wistar Rats ◽

Toxic Metal ◽

Bioinformatic Analysis ◽

Motor Dysfunction ◽

Motor Deficits ◽

Proteomic Profile ◽

Adult Rats

Lead (Pb) is a toxic metal with great neurotoxic potential. The aim of this study was to investigate the effects of a long-term Pb intoxication on the global proteomic profile, oxidative biochemistry and neuronal density in motor cortex of adult rats, and the possible outcomes related to motor functions. For this, Wistar rats received for 55 days a dose of 50 mg/Kg of Pb acetate by intragastric gavage. Then, the motor abilities were evaluated by open field and inclined plane tests. To investigate the possible oxidative biochemistry modulation, the levels of pro-oxidant parameters as lipid peroxidation and nitrites were evaluated. The global proteomic profile was evaluated by ultraefficiency liquid chromatography system coupled with mass spectrometry (UPLC/MS) followed by bioinformatic analysis. Moreover, it was evaluated the mature neuron density by anti-NeuN immunostaining. The statistical analysis was performed through Student’s t -test, considering p < 0.05 . We observed oxidative stress triggering by the increase in malonaldehyde and nitrite levels in motor cortex. In the proteomic analysis, the motor cortex presented alterations in proteins associated with neural functioning, morphological organization, and neurodegenerative features. In addition, it was observed a decrease in the number of mature neurons. These findings, associated with previous evidences observed in spinal cord, cerebellum, and hippocampus under the same Pb administration protocol, corroborate with the motor deficits in the rats towards Pb. Thus, we conclude that the long-term administration to Pb in young Wistar rats triggers impairments at several organizational levels, such as biochemical and morphological, which resulted in poor motor performance.

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iTRAQ protein profile analysis of Citrus sinensis roots in response to long-term boron-deficiency

Journal of Proteomics ◽

10.1016/j.jprot.2013.04.025 ◽

2013 ◽

Vol 93 ◽

pp. 179-206 ◽

Cited By ~ 106

Author(s):

Lin-Tong Yang ◽

Yi-Ping Qi ◽

Yi-Bin Lu ◽

Peng Guo ◽

Wen Sang ◽

...

Keyword(s):

Citrus Sinensis ◽

Profile Analysis ◽

Protein Profile ◽

Boron Deficiency

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Effects of Fluoride Long-Term Exposure over the Cerebellum: Global Proteomic Profile, Oxidative Biochemistry, Cell Density, and Motor Behavior Evaluation

International Journal of Molecular Sciences ◽

10.3390/ijms21197297 ◽

2020 ◽

Vol 21 (19) ◽

pp. 7297

Author(s):

Géssica Oliveira Lopes ◽

Maria Karolina Martins Ferreira ◽

Lodinikki Davis ◽

Leonardo Oliveira Bittencourt ◽

Walessa Alana Bragança Aragão ◽

...

Keyword(s):

Cell Density ◽

Motor Coordination ◽

Motor Behavior ◽

Exposure Period ◽

Peroxyl Radicals ◽

High Dose ◽

Proteomic Profile ◽

The Central Nervous System ◽

Therapeutic Doses

Although the literature does not provide evidence of health risks from exposure to fluoride (F) in therapeutic doses, questions remain about the effects of long-term and high-dose use on the function of the central nervous system. The objective of this study was to investigate the effect of long-term exposure to F at levels similar to those found in areas of artificial water fluoridation and in areas of endemic fluorosis on biochemical, proteomic, cell density, and functional parameters associated with the cerebellum. For this, mice were exposed to water containing 10 mg F/L or 50 mg F/L (as sodium fluoride) for 60 days. After the exposure period, the animals were submitted to motor tests and the cerebellum was evaluated for fluoride levels, antioxidant capacity against peroxyl radicals (ACAP), lipid peroxidation (MDA), and nitrite levels (NO). The proteomic profile and morphological integrity were also evaluated. The results showed that the 10 mg F/L dose was able to decrease the ACAP levels, and the animals exposed to 50 mg F/L presented lower levels of ACAP and higher levels of MDA and NO. The cerebellar proteomic profile in both groups was modulated, highlighting proteins related to the antioxidant system, energy production, and cell death, however no neuronal density change in cerebellum was observed. Functionally, the horizontal exploratory activity of both exposed groups was impaired, while only the 50 mg F/L group showed significant changes in postural stability. No motor coordination and balance impairments were observed in both groups. Our results suggest that fluoride may impair the cerebellar oxidative biochemistry, which is associated with the proteomic modulation and, although no morphological impairment was observed, only the highest concentration of fluoride was able to impair some cerebellar motor functions.

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Long-term boron-deficiency-responsive genes revealed by cDNA-AFLP differ between Citrus sinensis roots and leaves

Frontiers in Plant Science ◽

10.3389/fpls.2015.00585 ◽

2015 ◽

Vol 6 ◽

Cited By ~ 6

Author(s):

Yi-Bin Lu ◽

Yi-Ping Qi ◽

Lin-Tong Yang ◽

Jinwook Lee ◽

Peng Guo ◽

...

Keyword(s):

Citrus Sinensis ◽

Boron Deficiency

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A long-term study of early fluid therapy in severely burned adults. 3. Simultaneous comparison of saline solution alone or combined with plasma

JAMA ◽

10.1001/jama.195.4.268 ◽

1966 ◽

Vol 195 (4) ◽

pp. 268-274 ◽

Cited By ~ 4

Author(s):

M. Bocanegra

Keyword(s):

Fluid Therapy ◽

Saline Solution ◽

Term Study ◽

Long Term Study ◽

Simultaneous Comparison ◽

Early Fluid

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Therapy and prevention for mental health: What if mental diseases are mostly not brain disorders?

Behavioral and Brain Sciences ◽

10.1017/s0140525x1800105x ◽

2019 ◽

Vol 42 ◽

Cited By ~ 2

Author(s):

John P. A. Ioannidis

Keyword(s):

Mental Health ◽

Mental Disease ◽

Brain Disorders ◽

Social Stressors ◽

Labor Education ◽

Mental Diseases ◽

Long Term Follow Up ◽

Political Decisions

AbstractNeurobiology-based interventions for mental diseases and searches for useful biomarkers of treatment response have largely failed. Clinical trials should assess interventions related to environmental and social stressors, with long-term follow-up; social rather than biological endpoints; personalized outcomes; and suitable cluster, adaptive, and n-of-1 designs. Labor, education, financial, and other social/political decisions should be evaluated for their impacts on mental disease.

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