Testicular hyperthermia induces Unfolded Protein Response signaling activation in spermatocyte

Kim, Jung‐Hak; Park, Sun-Ji; Kim, Tae-Shin; Park, Hyo-Jin; Park, Junghyung; Kim, Bo Kyung; Kim, Gyeong-Ryul; Kim, Jin Man; Huang, Song; Chae, Jung‐Il; Park, Choon‐Keun; Lee, Dong Seok

doi:10.1016/j.bbrc.2013.04.032

Cited by 62 publications

(43 citation statements)

References 26 publications

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“…Two independent studies provide evidence that the toxic effects of endocrine-disrupting chemicals bisphenol-A and diethylstilbestrol and the major occupational and environmental toxicant cadmium on the testis are mediated by impairing ER homeostasis (Figure 4) via induction of IRE1α phosphorylation and CHOP expression in rat spermatozoa [107,108]. By comparison, activation of UPR signaling via enhanced levels of phosphorylated eIF2α, ATF4 and Growth arrest and DNA damage-inducible protein GADD34 (GADD34) and phospho-IRE1α induced XBP1s in response to testicular hyperthermia (43 °C, 15 min/day) as well as elevated ER stress-mediated spermatocyte apoptosis associated with CHOP, phosphorylated-c-Jun NH2-terminal kinases (P-JNK) and caspase-3 activity after repetitive periods of hyperthermia (Figure 4) have all been reported in the mouse testis [109]. In support of these observations, genetically induced excess ER stress as a result of GRP78 knockdown in the drosophila male accessory gland, which secretes seminal fluid proteins essential for reproduction, leads to increased XBP1s levels and results in male infertility [110].…”

Section: Upr Signaling Er Stress In Reproductive Physiopathologymentioning

confidence: 99%

Endoplasmic Reticulum Stress and Homeostasis in Reproductive Physiology and Pathology

Güzel

Arlıer

Guzeloglu‐Kayisli

et al. 2017

IJMS

199

131

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The endoplasmic reticulum (ER), comprises 60% of the total cell membrane and interacts directly or indirectly with several cell organelles i.e., Golgi bodies, mitochondria and proteasomes. The ER is usually associated with large numbers of attached ribosomes. During evolution, ER developed as the specific cellular site of synthesis, folding, modification and trafficking of secretory and cell-surface proteins. The ER is also the major intracellular calcium storage compartment that maintains cellular calcium homeostasis. During the production of functionally effective proteins, several ER-specific molecular steps sense quantity and quality of synthesized proteins as well as proper folding into their native structures. During this process, excess accumulation of unfolded/misfolded proteins in the ER lumen results in ER stress, the homeostatic coping mechanism that activates an ER-specific adaptation program, (the unfolded protein response; UPR) to increase ER-associated degradation of structurally and/or functionally defective proteins, thus sustaining ER homeostasis. Impaired ER homeostasis results in aberrant cellular responses, contributing to the pathogenesis of various diseases. Both female and male reproductive tissues undergo highly dynamic cellular, molecular and genetic changes such as oogenesis and spermatogenesis starting in prenatal life, mainly controlled by sex-steroids but also cytokines and growth factors throughout reproductive life. These reproductive changes require ER to provide extensive protein synthesis, folding, maturation and then their trafficking to appropriate cellular location as well as destroying unfolded/misfolded proteins via activating ER-associated degradation mediated proteasomes. Many studies have now shown roles for ER stress/UPR signaling cascades in the endometrial menstrual cycle, ovarian folliculogenesis and oocyte maturation, spermatogenesis, fertilization, pre-implantation embryo development and pregnancy and parturition. Conversely, the contribution of impaired ER homeostasis by severe/prolong ER stress-mediated UPR signaling pathways to several reproductive tissue pathologies including endometriosis, cancers, recurrent pregnancy loss and pregnancy complications associated with pre-term birth have been reported. This review focuses on ER stress and UPR signaling mechanisms, and their potential roles in female and male reproductive physiopathology involving in menstrual cycle changes, gametogenesis, preimplantation embryo development, implantation and placentation, labor, endometriosis, pregnancy complications and preterm birth as well as reproductive system tumorigenesis.

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Section: Upr Signaling Er Stress In Reproductive Physiopathologymentioning

confidence: 99%

Endoplasmic Reticulum Stress and Homeostasis in Reproductive Physiology and Pathology

Güzel

Arlıer

Guzeloglu‐Kayisli

et al. 2017

IJMS

199

131

View full text Add to dashboard Cite

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“…By using both mouse and human testis tissues, high GRP78 staining has reported in postmeiotic germ cells and spermatocytes with no staining in spermatogonium [67]. Additionally, while one cycle of hyperthermia induces survival mechanisms of UPR by activates PERK/eIF2α and IRE1α/XBP-1 branches, repetitive cycles of hyperthermia promote ER stress-mediated apoptosis through CHOP, phospho JNK, and caspase-3 activation [68].…”

Section: Er Stress Related Other Diseasesmentioning

confidence: 99%

Impact of high cholesterol and endoplasmic reticulum stress on metabolic diseases: An updated mini-review

2017

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Endoplasmic reticulum (ER) is the major site of protein folding and calcium storage. Beside the role of ER in protein homeostasis, it controls the cholesterol production and lipid-membrane biosynthesis as well as surviving and cell death signaling mechanisms in the cell. It is well-documented that elevated plasma cholesterol induces adverse effects in cardiovascular diseases (CVDs), liver disorders, such as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatosis hepatitis (NASH), and metabolic diseases which are associated with oxidative and ER stress. Recent animal model and human studies have showed high cholesterol and ER stress as an emerging factors involved in the development of many metabolic diseases. In this review, we will summarize the crucial effects of hypercholesterolemia and ER stress response in the pathogenesis of CVDs, NAFLD/NASH, diabetes and obesity which are major health problems in western countries.

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“…ERK, JNK, and p38-MAPK, key members of the MAPK superfamily, play major roles in cell apoptosis and survival 16. The JNK-p38-MAPK pathway is closely associated with Bcl-2 expression and the caspase cascade in spermatogenesis,3738 while the ERK signal pathway plays an important role in the activation of cellular processes involved in spermatogenesis including testicular heat shock and testicular torsion 3940. Here, we have further confirmed that JNK, p38-MAPK, and ERK could be activated by CaSR activation in testicular tissues from diabetic rats, in accordance with previous studies 2841.…”

Section: Discussionmentioning

confidence: 99%

The calcium-sensing receptor participates in testicular damage in streptozotocin-induced diabetic rats

et al. 2016

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Male infertility caused by testicular damage is one of the complications of diabetes mellitus. The calcium-sensing receptor (CaSR) is expressed in testicular tissues and plays a pivotal role in calcium homeostasis by activating cellular signaling pathways, but its role in testicular damage induced by diabetes remains unclear. A diabetic model was established by a single intraperitoneal injection of streptozotocin (STZ, 40 mg kg−1) in Wistar rats. Animals then received GdCl3 (an agonist of CaSR, 8.67 mg kg−1), NPS-2390 (an antagonist of CaSR, 0.20 g kg−1), or a combination of both 2 months after STZ injection. Diabetic rats had significantly lower testes weights and serum levels of testosterone compared to healthy rats, indicating testicular damage and dysfunction in STZ-induced diabetic rats. Compared with healthy controls, the testicular tissues of diabetic rats overexpressed the CaSR protein and had higher levels of malondialdehyde (MDA), lower superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity, and higher numbers of apoptotic germ cells. The testicular tissues from diabetic rats also expressed lower levels of Bcl-2 and higher levels of Bax and cleaved caspase-3 in addition to higher phosphorylation rates of c-Jun NH2-terminal protein kinase (JNK), p38, and extracellular signaling-regulated kinase (ERK) 1/2. The above parameters could be further increased or aggravated by the administration of GdCl3, but could be attenuated by injection of NPS-2390. In conclusion, the present results indicate that CaSR activation participates in diabetes-induced testicular damage, implying CaSR may be a potential target for protective strategies against diabetes-induced testicular damage and could help to prevent infertility in diabetic men.

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Testicular hyperthermia induces Unfolded Protein Response signaling activation in spermatocyte

Cited by 62 publications

References 26 publications

Endoplasmic Reticulum Stress and Homeostasis in Reproductive Physiology and Pathology

Endoplasmic Reticulum Stress and Homeostasis in Reproductive Physiology and Pathology

Impact of high cholesterol and endoplasmic reticulum stress on metabolic diseases: An updated mini-review

The calcium-sensing receptor participates in testicular damage in streptozotocin-induced diabetic rats

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