Excessive training is associated with endoplasmic reticulum stress but not apoptosis in the hypothalamus of mice

Pinto, Ana P.; Rocha, Aristides Almeida; Pereira, Bruno; Oliveira, Luís Guilherme de; Morais, Gustavo P.; Moura, Leandro Pereira de; Ropelle, Eduardo Rochete; Pauli, José Rodrigo; Silva, Adelino Sánchez Ramos da

doi:10.1139/apnm-2016-0542

Cited by 11 publications

(12 citation statements)

References 32 publications

(61 reference statements)

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“…Regarding ATF6, mRNA levels were not changed in rat liver with the 6-week treadmill (Chapados & Lavoie, 2010). The same results were obtained in ATF6 levels in mice hypothalamus after 8-week voluntary running (Pinto et al, 2017). This could be explained by the fact that BiP levels depend on those of ATF6 (Borsa et al, 2015), which, in our case, was not increased by exercise.…”

Section: Discussionsupporting

confidence: 85%

Effects of a resistance‐training programme on endoplasmic reticulum unfolded protein response and mitochondrial functions in PBMCs from elderly subjects

Estébanez

Moreira

Almar

et al. 2019

European Journal of Sport Science

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Aging has been related with a decline in the ability to handle protein folding, which leads to endoplasmic reticulum stress and alterations in unfolded protein response (UPR). Importantly, physical activity could activate the UPR and attenuate or prevent age-induced ER dysfunction. The current study evaluated the effects of a resistance exercise on UPR and mitochondrial functions in peripheral blood mononuclear cells (PBMCs) from elderly subjects. Thirty healthy women and men (age, 72.8, s x− = 2.2 years) were randomized to a training group, which performed an 8-week resistance training programme, or a control group, which followed their daily routines. The phosphorylation of PERK and IRE1a, as well as ATF4, and XBP1 protein expression, significantly increased following the training, while expression of BiP, AFT6 and CHOP remain without changes. Additionally, the intervention also induced an increase in PGC-1a and Mfn1 protein levels, while no changes were found in Drp1 expression. Finally, the resistance protocol was not able to activate PINK1/ Parkin and Bnip3/Nix pathways. The results obtained seem to indicate that 8-week resistance exercise activates the UPR, stimulates mitochondrial biogenesis, maintains mitochondrial dynamics and prevents mitophagy activation by unfolded proteins in PBMCs from elderly subjects AQ2 ¶ .

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Section: Discussionsupporting

confidence: 85%

Effects of a resistance‐training programme on endoplasmic reticulum unfolded protein response and mitochondrial functions in PBMCs from elderly subjects

Estébanez

Moreira

Almar

et al. 2019

European Journal of Sport Science

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“…46,53 Thus, the increase in cardiac glycogen deposition after the 3 overtraining models may be considered a compensatory mechanism for the impairment of skeletal muscle signal transduction. 12,18 Because our overtraining models led to decreased performance and other negative responses in different tissues, 11,12,21,24,26,29,54,55 it is important to point out that upregulation of insulin signaling pathway components in mice hearts is also related to pathologic hypertrophy. [56][57][58] Therefore, further studies should evaluate whether these overtraining models lead to pathologic or physiologic cardiac hypertrophy.…”

Section: Resultsmentioning

confidence: 99%

Excessive treadmill training enhances the insulin signaling pathway and glycogen deposition in mice hearts

Oliveira

Morais

Rocha

et al. 2018

J of Cellular Biochemistry

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Exhaustive and chronic physical exercise leads to peripheral inflammation, which is one of the molecular mechanisms responsible for the impairment of the insulin signaling pathway in the heart. Recently, 3 different running overtraining models performed downhill (OTR/down), uphill (OTR/up), and without inclination (OTR) increased the serum levels of proinflammatory cytokines. This proinflammatory status induced insulin signaling impairment in the skeletal muscle; however, the response of this signaling pathway in the cardiac muscle of overtrained mice was still unknown. Thus, we investigated the effects of OTR/down, OTR/up, and OTR protocols on the protein levels of phosphorylation of insulin receptor β (pIRβ) (Tyr), phosphorylation of protein kinase B (pAkt) (Ser473), plasma membrane glucose transporter‐1 (GLUT1) and GLUT4, phosphorylation of insulin receptor substrate‐1 (pIRS‐1) (Ser307), phosphorylation of IκB kinase α/β) (pIKKα/β (Ser180/181), phosphorylation of p38 mitogen‐activated protein kinase (p‐p38MAPK) (Thr180/Tyr182), phosphorylation of stress‐activated protein kinases‐Jun amino‐terminal kinases (pSAPK‐JNK) (Thr183/Tyr185), and glycogen content in mice hearts. The rodents were divided into naïve (N, sedentary mice), control (CT, sedentary mice submitted to performance evaluations), trained (TR, performed the training protocol), OTR/down, OTR/up, and OTR groups. After the grip force test, the cardiac muscles (ie, left ventricle) were removed and used for immunoblotting and histology. Although the OTR/up and OTR groups exhibited higher cardiac levels of pIRβ (Tyr), only the OTR group exhibited higher cardiac levels of pAkt (Ser473) and plasma membrane GLUT4. On the contrary, the OTR/down group exhibited higher cardiac levels of pIRS‐1 (Ser307). The OTR model enhanced the cardiac insulin signaling pathway. All overtraining models increased the left ventricle glycogen content, with this probably acting as a compensatory organ in response to skeletal muscle insulin signaling impairment.

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“…In a study based in 3-weeks voluntary running with mice fed low-fat diet (LFD) or HFD, eIF2α mRNA expression was upregulated in brain and liver of high runners with both LFD and HFD, while peIF2α only increased in hippocampus of HFD-high runners (Kim et al, 2010). Similarly, 8-weeks running with different inclinations demonstrated that the downhill protocol increased peIF2α levels in mice EDL (Pereira et al, 2016) and hypothalamus (Pinto et al, 2017). By the contrary, 8-weeks swimming decreased peIF2α in HFD rat liver and AT, but not in control rats (da Luz et al, 2011).…”

Section: Exercise and Uprmentioning

confidence: 93%

“…Thus, 6-weeks endurance training increased PERK levels in mice soleus and liver (Deldicque et al, 2013) and 3-weeks running increased ATF6 mRNA expression in mice brain (Kim et al, 2010). Finally, 8-weeks running in downhill, uphill, or without inclination modified pPERK, pIRE1, and ATF6 levels in mice hypothalamus and muscles (Pereira et al, 2016; Pinto et al, 2017). However, contradictory results were also found in the two previous studies, depending on the tissue and the type of protocol employed.…”

Section: Exercise and Uprmentioning

confidence: 99%

Endoplasmic Reticulum Unfolded Protein Response, Aging and Exercise: An Update

et al. 2018

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The endoplasmic reticulum (ER) is a dynamic and multifunctional organelle responsible for protein biosynthesis, folding, assembly and modifications. Loss of protein folding regulation, which leads to unfolded or misfolded proteins accumulation inside the ER lumen, drives ER stress (ERS) and unfolded protein response (UPR) activation. During aging, there is a decline in the ability of the cell to handle protein folding, accumulation and aggregation, and the function of UPR is compromised. There is a progressive failure of the chaperoning systems and a decline in many of its components, so that the UPR activation cannot rescue the ERS. Physical activity has been proposed as a powerful tool against aged-related diseases, which are linked to ERS. Interventional studies have demonstrated that regular exercise is able to decrease oxidative stress and inflammation and reverse mitochondrial and ER dysfunctions. Exercise-induced metabolic stress could activate the UPR since muscle contraction is directly involved in its activation, mediating exercise-induced adaptation responses. In fact, regular moderate-intensity exercise-induced ERS acts as a protective mechanism against current and future stressors. However, biological responses vary according to exercise intensity and therefore induce different degrees of ERS and UPR activation. This article reviews the effects of aging and exercise on ERS and UPR, also analyzing possible changes induced by different types of exercise in elderly subjects.

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Excessive training is associated with endoplasmic reticulum stress but not apoptosis in the hypothalamus of mice

Cited by 11 publications

References 32 publications

Effects of a resistance‐training programme on endoplasmic reticulum unfolded protein response and mitochondrial functions in PBMCs from elderly subjects

Effects of a resistance‐training programme on endoplasmic reticulum unfolded protein response and mitochondrial functions in PBMCs from elderly subjects

Excessive treadmill training enhances the insulin signaling pathway and glycogen deposition in mice hearts

Endoplasmic Reticulum Unfolded Protein Response, Aging and Exercise: An Update

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