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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
Received: 26 April 2020/Accepted: 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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*Corresponding
author; email: nurulfarhana@ukm.edu.my
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