Sains Malaysiana 50(5)(2021): 1415-1424

http://doi.org/10.17576/jsm-2021-5005-20

 

Potensi Pembangunan Kajian Autofagi dalam Fungsi Endotelium Otak Manusia

(Development Potential of Autophagy Studies in the Human Brain Endothelium Functions)

 

NURUL FARHANA JUFRI*, SITI NURDIYANA MOHD SALEH, NOR ATIKAH SAFIRAH JUHARI, FARAH WAHIDA IBRAHIM & ASMAH HAMID

 

Program Sains Bioperubatan, Pusat Kajian Toksikologi dan Risiko Kesihatan (CORE), Fakulti Sains Kesihatan, Universiti Kebangsaan Malaysia, 50300 Kuala Lumpur, Wilayah Persekutuan, Malaysia

 

Diserahkan: 26 April 2020/Diterima: 30 September 2020

 

ABSTRAK

Autofagi adalah proses fisiologi yang terlibat dalam penggantian komponen sel dan berfungsi sebagai mekanisme kelangsungan hidup sementara semasa kebuluran sel akibat kekurangan sumber makanan. Proses ini melibatkan tapak jalan lisosom yang menguraikan bahan yang terdapat dalam sitoplasma seperti organel dan makromolekul. Keberlangsungan proses autofagi bergantung kepada fungsi normal lisosom untuk mengurai dan mengitar semula bahan yang terkumpul di dalam autofagosom. Kegagalan fungsi pada lisosom akan mempengaruhi fungsi autofagi. Secara in vitro, proses autofagi boleh direncat dengan menggunakan bahan kimia seperti amonium klorida yang akan mengganggu fungsi lisosom melalui peningkatan pH lisosom yang seterusnya menghalang keberkesanan enzim lisosom. Hal ini akan menyebabkan kandungan di dalam autofagosom tidak dapat diurai dan meningkatkan penimbunan autofagosom yang mengandungi protein yang rosak. Penimbunan protein yang rosak ini telah dikenal pasti sebagai salah satu patogenesis penyakit neurodegenerasi yang kini dikaitkan dengan ketidakfungsian sel endotelium di otak. Perencatan tapak jalan autofagi-lisosom ini akan menyebabkan gangguan pembentukan struktur autofagi dan lisosom yang seterusnya menyebabkan peningkatan atau penurunan ekspresi protein seperti LC3 dan p62 yang terlibat dalam tapak jalan ini. ICAM-1, eNOS dan Claudin-5 pada sel endotelium merupakan antara penanda yang berpotensi digunakan dalam pengenalpastian ketidakfungsian yang mungkin berlaku pada sel endotelium otak manusia.

 

Kata kunci: Autofagosom; disfungsi sel endotelium; ketidakfungsian; lisosom; sel endotelium

 

ABSTRACT

Autophagy is a physiological process involved in replacing cellular components and function as a temporary survival mechanism during cell starvation. This process involves lysosomal pathway that degrades materials contained in the cytoplasm such as organelles and macromolecules. The occurrence of the autophagy process depends on normal lysosomal function which degrades and recycles accumulated cellular material in autophagosome. Lysosome dysfunction will eventually affects autophagy function. In in vitro, autophagy can be inhibited by using chemical such as ammonium chloride which will disturb lysosome function by increasing lysosome's pH hence hindering the effectiveness of lysosomal enzymes. This prevents autophagosomal content degradation, thus, leading to the accumulation of autophagosomes containing defective proteins. Accumulation of the defective proteins has been identified as one of the pathogenesis in neurodegenerative diseases which now is linked with endothelial dysfunction. Inhibition of this autophagy-lysosome pathway results in disruption of the formation of autophagy and lysosome structures that leads to the increase or decrease in protein expressions involved in this pathway such as LC3 and p62. Other markers such as ICAM-1, eNOS, and Claudin-5 in endothelial cell are among potential markers to be used in identification of dysfunction that may happen in context of human brain endothelial cell.

 

Keywords: Autophagosome; endothelial cell; endothelial dysfunction; lysosome

 

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*Pengarang untuk surat-menyurat; email: nurulfarhana@ukm.edu.my

 

 

 

 

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