Hyperhomocysteinemia Transcriptionally Regulates Expression of a Set of Ion Channels in Brain and Heart Tissues in Mice

Year 2024, , 12 - 19, 30.04.2024

Ebru Önalan , İlay Buran Kavuran , Ahmet Tektemur , Esin Öz , Seda Özaydın , Arzu Etem Akağaç , Ramazan Bal

https://doi.org/10.47572/muskutd.1347282

Abstract

The alterations of ion channel gene expressions in brain and heart tissues in HHcy have not been previously reported. We investigated the mRNA expression levels in brain and heart tissues of the HHcy mice compared to the control mice to characterize distinct expression of 36 ion channels. C57BL/6 J. mice were divided into two groups of 15 animals each: (1) control group and (2) HHcy group. The HHcy was induced by methionine administiration. The mRNA levels of ion channels were analyzed using qRT-PCR. TUNEL staining and MDA assay were used for verification of the negative side effects of HHcy in heart and brain tissues. RT-PCR revealed the upregulation of Hcn4, Trpc3, Trpm2 and the downregulation of Abbc8, Cacna1b, Cacna1c, Cacna1e, Cacna1h, Hcn1, Kcnc3, Kcnh7, Kcnj8, Trpc4, Trpc5, Trpc6, Trpm3, Trpm4, Trpv4, Trpv6 in brain tissues of the HHcy group compared to the control. The upregulation of ion channel expressions in heart tissues were not detected, but we found only the downregulation of Accn1, Accn2, Accn3, Hcn1, Kcnc4 and Trpv6 ion channels. Apoptozis and MDA level were significantly increased in brain and heart tissues of the HHcy group compared to the control. Brain tissues compared to heart tissues exhibit a very considerable and diverse ion channel gene expression pattern in mice with HHcy than control. Clarifying the roles of ion channels in HHcy could shed light on the development of novel therapeutic strategies and ultimately improve HHcy side effects.

Keywords

Acid-Sensing Ion Channels, Transient Receptor Potential Channels, Hyperhomocysteinemia, Calcium Channels, Potassium Channels

Supporting Institution

Firat University Scientific Research Unit (FUBAP)

Project Number

TF.11.67

Thanks

We thank to the Firat University Scientific Research Unit (FUBAP) for funding this Project (Project Grant No: TF.11.67)

Hiperhomosisteinemi, Farelerde Beyin ve Kalp Dokularında Bir İyon Kanalları Kümesinin Ekspresyonunu Transkripsiyonel Olarak Düzenler

Abstract

Hiperhomosisteinemide (HHcy) beyin ve kalp dokularındaki iyon kanalı gen ifadelerindeki değişiklikler daha önce bildirilmemiştir. Araştırmamızda HHcy farelerinin beyin ve kalp dokularındaki 36 iyon kanalının ekspresyonunu karakterize etmek için kontrol fareleri ile kıyasladık. C57BL/6 J. fareleri, her biri 15 hayvandan oluşan iki gruba ayrıldı: (1) kontrol ve (2) HHcy grubu. HHcy, metiyonin uygulamasıyla indüklendi. İyon kanallarının mRNA seviyeleri, qRT-PCR kullanılarak analiz edildi. HHcy'nin kalp ve beyin dokularındaki olumsuz yan etkilerini doğrulamak için TUNEL boyama ve MDA testi kullanıldı. RT-PCR sonuçlarına göre kontrol ile karşılaştırıldığında HHcy grubunun beyin dokularında Hcn4, Trpc3, Trpm2'nin ifadesinin arttığı ve Abbc8, Cacna1b, Cacna1c, Cacna1e, Cacna1h, Hcn1, Kcnc3, Kcnh7, Kcnj8, Trpc4, Trpc5, Trpc6, Trpm3, Trpm4, Trpv4, Trpv6'nın ifadesinin azaldığı belirlendi. Kalp dokularında iyon kanalı ifadelerinde artış tespit edilmedi ancak Accn1, Accn2, Accn3, Hcn1, Kcnc4 ve Trpv6 iyon kanallarının ifadesinin azaldığı bulundu. HHcy grubunun beyin ve kalp dokularında apoptozis ve MDA düzeyinin kontrole göre anlamlı olarak yüksek olduğu belirlendi. Kalp dokularıyla karşılaştırıldığında beyin dokuları, HHcy'li farelerde kontrole göre çok önemli ve çeşitli bir iyon kanalı gen ekspresyon paterni sergiler. İyon kanallarının HHcy'deki rollerinin açıklığa kavuşturulması, yeni terapötik stratejilerin geliştirilmesine ışık tutabilir ve sonuçta HHcy yan etkilerini iyileştirebilir.

Keywords

Asit Duyarlı İyon Kanalları, Geçici Reseptör Potansiyel Kanalları, Hiperhomosisteinemi, Kalsiyum Kanalları, Potasyum Kanalları

Project Number

TF.11.67

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