HSPA1L and HSPA1B gene polymorphisms and haplotypes are associated with idiopathic male infertility in Iranian population

Kohan, Leila; Tabiee, Omid; Sepahi, Neda

doi:10.1016/j.ejogrb.2019.06.014

Cited by 7 publications

(10 citation statements)

References 33 publications

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“…It typically starts to express from step 12 spermatids of stage I spermatogenesis. Previously, it was thought to have important functions in spermatogenesis and was therefore associated with an increased risk of idiopathic male infertility (Kohan, Tabiee & Sepahi, 2019). However, our studies demonstrate that Hspa1l −/− Hspa1l −/− mice have normal spermatogenesis with appearance of all types and stages of spermatogenic cells.…”

Section: Discussioncontrasting

confidence: 56%

“…Unlike Hspa1a and Hspa1b, Hspa1l is constitutively expressed, and is highly abundant in the testis (Daugaard, Rohde & Jaattela, 2007;Radons, 2016). The mutations of Hspa1l is supposed to be associated with inflammatory bowel disease, an increased risk of male infertility and spontaneous preterm births (Ciftci et al, 2015;Huusko et al, 2018;Kohan, Tabiee & Sepahi, 2019;Takahashi et al, 2017). HSPA1L has been thought to play important functions in testis similar to HSPA2 (Tsunekawa et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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The heat shock protein family geneHspa1lin male mice is dispensable for fertility

Wang

Xie

Yao

et al. 2020

PeerJ

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Background Heat shock protein family A member 1 like (Hspa1l) is a member of the 70kD heat shock protein (Hsp70) family. HSPA1L is an ancient, evolutionarily conserved gene with a highly conserved domain structure. The gene is highly abundant and constitutively expressed in the mice testes. However, the role of Hspa1l in the testes has still not been elucidated. Methods Hspa1l-mutant mice were generated using the CRISPR/Cas9 system. Histological and immunofluorescence staining were used to analyze the phenotypes of testis and epididymis. Apoptotic cells were detected through TUNEL assays. Fertility and sperm motilities were also tested. Quantitative RT-PCR was used for analyzing of candidate genes expression. Heat treatment was used to induce heat stress of the testis. Results We successfully generated Hspa1l knockout mice. Hspa1l-/- mice exhibited normal development and fertility. Further, Hspa1l-/- mice shown no significant difference in spermatogenesis, the number of apoptotic cells in testes epididymal histology, sperm count and sperm motility from Hspa1l+/+ mice. Moreover, heat stress does not exacerbate the cell apoptosis in Hspa1l-/- testes. These results revealed that HSPA1L is not essential for physiological spermatogenesis, nor is it involved in heat-induced stress responses, which provides a basis for further studies.

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Section: Discussioncontrasting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

The heat shock protein family geneHspa1lin male mice is dispensable for fertility

Wang

Xie

Yao

et al. 2020

PeerJ

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“…HSPA1L is highly and constitutively expressed in male germ lines and protects male germ cells from external stresses such as heat and oxidative stress [24,25]. Therefore, HSPA1L gene polymorphisms in the region encoding the client-binding domain are reported to be associated with diseases such as male infertility [26,27]. However, its detailed functions are unclear.…”

Section: Introductionmentioning

confidence: 99%

HSPA1L Enhances Cancer Stem Cell-Like Properties by Activating IGF1Rβ and Regulating β-Catenin Transcription

Choi

Lee

Kim

et al. 2020

IJMS

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Studies have shown that cancer stem cells (CSCs) are involved in resistance and metastasis of cancer; thus, therapies targeting CSCs have been proposed. Here, we report that heat shock 70-kDa protein 1-like (HSPA1L) is partly involved in enhancing epithelial–mesenchymal transition (EMT) and CSC-like properties in non-small cell lung cancer (NSCLC) cells. Aldehyde dehydrogenase 1 (ALDH1) is considered a CSC marker in some lung cancers. Here, we analyzed transcriptional changes in genes between ALDH1high and ALDH1low cells sorted from A549 NSCLC cells and found that HSPA1L was highly expressed in ALDH1high cells. HSPA1L played two important roles in enhancing CSC-like properties. First, HSPA1L interacts directly with IGF1Rβ and integrin αV to form a triple complex that is involved in IGF1Rβ activation. HSPA1L/integrin αV complex-associated IGF1Rβ activation intensified the EMT-associated cancer stemness and γ-radiation resistance through its downstream AKT/NF-κB or AKT/GSK3β/β-catenin activation pathway. Secondly, HSPA1L was also present in the nucleus and could bind directly to the promoter region of β-catenin to function as a transcription activator of β-catenin, an important signaling protein characterizing CSCs by regulating ALDH1 expression. HSPA1L may be a novel potential target for cancer treatment because it both enhances IGF1Rβ activation and regulates γβ-catenin transcription, accumulating CSC-like properties.

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“…They represent the major cytoplasmic heat-inducible Hsp70s. 49 It would be very difficult to differentiate these two isoforms using standard techniques such as immunoblotting or quantitative polymerase chain reaction (PCR). As a result, it is challenging to assign a function to one of these isoforms independently.…”

Section: Hsp70 Isoforms In Humansmentioning

confidence: 99%

“…HspA1A and HspA1B are the most highly conserved Hsp70s in humans, differing by only two amino acids. They represent the major cytoplasmic heat-inducible Hsp70s . It would be very difficult to differentiate these two isoforms using standard techniques such as immunoblotting or quantitative polymerase chain reaction (PCR).…”

Section: Hsp70 Isoforms In Humansmentioning

confidence: 99%

Function, Therapeutic Potential, and Inhibition of Hsp70 Chaperones

Ambrose

Chapman

2021

J. Med. Chem.

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Hsp70s are among the most highly conserved proteins in all of biology. Through an iterative binding and release of exposed hydrophobic residues on client proteins, Hsp70s can prevent aggregation and promote folding to the native state of their client proteins. The human proteome contains eight canonical Hsp70s. Because Hsp70s are relatively promiscuous they play a role in folding a large proportion of the proteome. Hsp70s are implicated in disease through their ability to regulate protein homeostasis. In recent years, researchers have attempted to develop selective inhibitors of Hsp70 isoforms to better understand the role of individual isoforms in biology and as potential therapeutics. Selective inhibitors have come from rational design, forced localization, and serendipity, but the development of completely selective inhibitors remains elusive. In the present review, we discuss the Hsp70 structure and function, the known Hsp70 client proteins, the role of Hsp70s in disease, and current efforts to discover Hsp70 modulators.

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HSPA1L and HSPA1B gene polymorphisms and haplotypes are associated with idiopathic male infertility in Iranian population

Cited by 7 publications

References 33 publications

The heat shock protein family geneHspa1lin male mice is dispensable for fertility

The heat shock protein family geneHspa1lin male mice is dispensable for fertility

HSPA1L Enhances Cancer Stem Cell-Like Properties by Activating IGF1Rβ and Regulating β-Catenin Transcription

Function, Therapeutic Potential, and Inhibition of Hsp70 Chaperones

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