1kits (Ebipipa 10) .
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▎ SS-31 kye ki?
SS-31 ye peptide ya molekyu entono ekolebwa amino asidi nnya. Kirimu amino asidi ez’ekika kya D ekitundu, kiraga okuziyiza okw’amaanyi okuvunda kwa protease, era era peptide eyingira mu butoffaali. Nga phospholipase A2 inhibitor ne mitochondrial-targeted peptide, SS-31 mu ngeri ey’enjawulo ekuŋŋaanyizibwa ku mitochondrial membrane ey’omunda era n’ekola ebikolwa byayo okuyita mu nkola eziwera.
▎ Enzimba ya SS-31
Ensibuko: PubChem |
Omutendera: RXKF Ensengekera ya molekyu: C 32H 49N 9O5 Obuzito bwa molekyu: 639.8g/mol Ennamba ya CAS: 736992-21-5 PubChem CID: 11764719. Omuntu w’abantu Ebigambo ebifaanagana: Elamipretide |
▎ SS-31 Okunoonyereza
Ensibuko y’okunoonyereza eya SS-31 eri etya?
SS-31 ye peptide ya opioid eggibwa mu peptide ya pheromone. Yasooka kuzuulibwa mu kiseera ky’okunoonyereza okw’enkola ku pheromone peptide, eraga ebikolwa eby’amaanyi eby’okukendeeza obulumi n’okuyita obulungi mu luwuzi lw’obutoffaali, ekivaako okuzuula peptide SS-311 egenderera mitochondrial-targeted antioxidant peptide. Ensibuko yaayo ey’okunoonyereza era ekwatagana nnyo n’okunoonyereza ku ndwadde ezikwatagana n’obutakola bulungi bwa mitochondria. Nga 'powerhouse' y'obutoffaali, obutakola bulungi bwa mitochondrial bukwatagana n'okutandika n'okukulaakulana kw'endwadde ez'enjawulo, gamba nga ischemia-reperfusion injury, endwadde z'obusimu, okulemererwa kw'omutima, n'okukaddiwa kw'ebinywa, byonna bikwatagana n'okunyigirizibwa okw'okwokya (oxidative stress) okuva ku kukola ebisusse ebiyitibwa free radicals. SS-31 ekendeeza bulungi ku situleesi y’okwokya (oxidative stress) era ekuuma enkola ya mitochondria.
Enkola ki ey’okukola kwa SS-31?
Okulungamya eby’amasannyalaze eby’okungulu kw’olususu:
SS-31 ekwatagana n’oluwuzi lwa mitochondrial, n’ekyusa eby’amasannyalaze eby’okungulu kw’oluwuzi okufuga ensaasaanya ya ion ne puloteyina ezisookerwako ku nsengekera y’oluwuzi. Okunoonyereza kulaga nti SS-31 esobola okukyusa ensaasaanya ya divalent cations mu kitundu ekikwatagana n’olususu, bwe kityo n’ekendeeza ku buzito bw’amasoboza ag’okunyigirizibwa kwa kalisiyamu mu mitochondrial n’okukuuma obutebenkevu bw’oluwuzi lwa mitochondrial [1,2]..
Okukwata ku nteekateeka y’amasavu:
Peptide eno esobola okuleeta enkyukakyuka ezidda emabega mu nteekateeka y’amasavu. Newankubadde nga tekitaataaganya kutebenkera kwa bilayer ku bungi bw’okusiba, kiyinza okukwata mu ngeri etali butereevu enkola z’omubiri ezikwatagana n’oluwuzi lwa mitochondrial, gamba ng’enkola ya puloteyina y’olususu n’okutambula kw’olususu, bwe kityo ne kikola ekirungi ku nkola ya mitochondria [1,2]..
Okuziyiza okuddamu kw’okuzimba:
Mu kunoonyereza okukwata ku sepsis, SS-31 yazuulibwa nti ekendeeza ku nsonga ezizimba nga interleukin-6 (IL-6), interleukin-1β (IL-1β), ne tumor necrosis factor -α (TNF-α), bwe kityo n’ekendeeza ku kwonooneka okuva mu kuddamu kw’okuzimba ku bitundu n’ebitundu by’omubiri [3]..
Okukendeeza ku situleesi y’okwokya:
SS-31 esobola okutumbula emirimu gy’enziyiza eziziyiza obuwuka obuleeta obulwadde nga superoxide dismutase (SOD) ne glutathione peroxidase, okukendeeza ku miwendo gy’ebintu ebiziyiza obuwuka obuleeta obulwadde nga malondialdehyde (MDA), n’okukendeeza ku kukola ebika bya oxygen ebikola (ROS), bwe kityo n’ekendeeza ku kwonooneka kw’obutoffaali n’ebitundu ebiva ku situleesi y’okwokya n’okukuuma emirimu egya bulijjo egya mitochondria n’obutoffaali [3] . .
Okulungamya enkyukakyuka ya mitochondria:
Mu kunoonyereza ku sepsis-associated encephalopathy, SS-31 esobola okuziyiza okukola okuyitiridde kwa mitochondrial fission-related proteins nga dynamin-related protein 1 (Drp1), okukendeeza ku mitochondrial fission okuyitiridde, okukuuma enkula ya mitochondrial eya bulijjo n’enkola, era bwe kityo okulongoosa enkola y’okutegeera [4]. .

Ekifaananyi 1. Enkola y’okukuŋŋaanyizibwa n’okuziyiza obuwuka obuleeta obulwadde bwa Szeto-Schiller-31 (SS-31) [5] ..
Ensibuko: MDPI
Mirimu ki n’enkozesa ya SS-31?
Emirimu
Ebikolwa by’okukuuma obutoffaali:
Mu nkola ya hydrogen peroxide (H2O2) induced oxidative stress damage model of ARPE-19 cells, SS-31 esobola okwongera ku cell survival rate, okukendeeza intracellular ROS content, okukuuma mitochondrial membrane potential, n’okukendeeza ku cell death rate, okulaga ebikolwa eby’obukuumi ebinene ku cells eyonoonese oxidative stress.
Okulongoosa enkola y’ebitundu by’omubiri
Omutima: Mu bikolwa by’ebisolo eby’obuvune obuva ku myocardial ischemia-reperfusion, okusooka okujjanjabwa ne SS-31 nga tebannaba kuddamu kussa musaayi kwakendeeza nnyo ku sayizi y’okusannyalala kw’omusuwa gw’omutima, ng’obulungi bukwatagana bulungi n’obuzibu bw’okusannyalala kw’omusuwa gw’omutima; mu kiseera ky’okusannyalala, SS-31 yakendeeza ku kitundu ekitaliimu kukulukuta mu kitundu ky’omusuwa gw’omutima ekya hypoperfused era n’elongoosa emirundi n’obuzibu bw’okutambula kw’omusaayi. Mu buzibu bw’emisuwa gy’omutima obuva ku sepsis, SS-31 esobola okuzzaawo okwonooneka kw’enkula y’emisuwa gy’omutima, okuziyiza okuddamu kw’okuzimba, okulongoosa ebbula ly’amaanyi g’emisuwa gy’omutima, okukuuma obusobozi bw’oluwuzi lw’emisuwa gy’omutima, n’okukuuma omutima obutakosebwa [3]..
Amawuggwe: SS-31 esobola okukendeeza ku kuzimba n’okuzimba mu bitundu by’amawuggwe, okukendeeza ku bubonero bw’amawuggwe mu bitundu by’amawuggwe, okutereeza ensonga z’okuzimba n’ebiraga ebikwata ku situleesi y’okwokya, n’okulongoosa obuvune bw’amawuggwe obw’amaanyi.
Obwongo: Okukuba empiso ya SS-31 mu lubuto obutasalako kisobola okulongoosa enkola y’okutegeera n’omutindo gw’okuwangaala mu mbeba, okukendeeza ku kuzimba kwa hippocampal, okukola ROS, n’okugabanya kwa mitochondrial hyperdivision. Mu model y’ebibe eby’emyaka, obujjanjabi bwa SS-31 buleeta enkyukakyuka mu microvascular proteome of the cerebral cortex, okukosa okwolesebwa kwa puloteyina ezikwatagana ne mitochondrial, era nga bulina ekikolwa ekimu eky’okulongoosa ku nkyukakyuka z’emisuwa emitonotono ezeekuusa ku myaka mu bwongo [4,6]..
Okusaba
Endwadde z’emisuwa n’emisuwa:
Okusinziira ku bikolwa byayo eby’obukuumi ku buvune bw’emisuwa gy’omutima-reperfusion n’obuzibu bw’emisuwa gy’omutima obuva ku sepsis, SS-31 erina omugaso oguyinza okukozesebwa mu kuziyiza n’okujjanjaba endwadde z’emisuwa, ng’esobola okukolebwa ng’ekirungo ekipya eky’obujjanjabi eri embeera ng’okusannyalala kw’emisuwa gy’omutima ne sepsis-induced cardiomyopathy [3] ..
Endwadde z’amawuggwe:
Ku buvune obw’amawuggwe obuva ku sepsis, SS-31 eyinza okukola ng’ekirungo ekirungi eky’obujjanjabi ng’ekendeeza ku kuzimba n’okunyigirizibwa okw’okwokya, bwe kityo n’elongoosa enkola y’amawuggwe n’okuwa obujjanjabi obupya eri abalwadde abalina obuvune obw’amaanyi mu mawuggwe.
Endwadde z’obusimu:
Mu bulwadde bw’obwongo obukwatagana ne sepsis n’endwadde z’obusimu ezeekuusa ku myaka, SS-31 eraga obusobozi okulongoosa enkola y’okutegeera, ekiraga nti esobola okukulaakulana mu kujjanjaba endwadde z’obusimu nga Alzheimer n’okukosa okutegeera oluvannyuma lw’okukwatibwa sepsis [4,6]..
Obulwadde bw’emisuwa:
Olw’ebikolwa byayo eby’obujjanjabi ku nvunza eziyitibwa ApoE gene-knockout atherosclerotic rats, SS-31 erina obusobozi okukozesebwa mu kujjanjaba endwadde z’emisuwa nga ekendeeza ku situleesi y’okwokya n’okukendeeza ku kukula kw’obulwadde.
Mu bufunzi
Mu bufunze, SS-31 ye mitochondrial-targeted antioxidant peptide etereeza eby’amasannyalaze eby’okungulu kw’olususu, eziyiza okuzimba, ekendeeza ku oxidative stress, era elongoosa mitochondrial dynamics. Kikuuma ebitundu by’omubiri ng’omutima, amawuggwe, n’obwongo, kikendeeza ku buvune obuva ku ischemia-reperfusion n’okwonooneka okwekuusa ku sepsis, kilwawo okukaddiwa kw’obutoffaali, era kirina ebikolwa ebimu eby’obujjanjabi mu kuziyiza n’okujjanjaba endwadde z’emisuwa, obusimu, n’endala ez’enkola, awamu n’okuzimba emisuwa.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal
Broome, Sophie C akwatagana ne Yunivasite y’Abakatuliki mu Australia ne Yunivasite y’e Auckland. Okunoonyereza kwe kukwata ku bintu ebiwerako, omuli Sport Sciences, Physiology, Nutrition & Dietetics, Biochemistry & Molecular Biology, ne Neurosciences & Neurology. Anoonyereza ku bikolwa bya dduyiro ku nkola y’omubiri n’obulamu, n’akebera engeri omubiri gy’addamu n’okukyusakyusa mu kukola emirimu gy’omubiri. Broome era anoonyereza ku nkolagana wakati w’endya n’obulamu, n’enkozesa ya biochemistry ne molecular biology mu ssaayansi wa dduyiro. Omulimu gwe mu sayansi w’obusimu n’obusimu gwongera okwongera ku kutegeera kwaffe ku nkola y’obusimu n’obuzibu obukwatagana nabyo, ne tuwa amagezi ag’omuwendo ag’enzikiriziganya n’enkola ku ssaayansi w’emizannyo n’okunoonyereza ku by’obulamu. Broome, Sophie C awandiikiddwa mu kiwandiiko ekijuliziddwa [5].
▎ Ebiwandiiko Ebikwatagana
[1] Mitchell W, Ng E. A., Tamucci J. D., n’abalala. Peptide SS-31 egendereddwamu mitochondria esiba lipid bilayers era n’ekyusakyusa amasannyalaze ag’okungulu ng’ekitundu ekikulu eky’enkola yaayo ey’okukola[J]. Journal of Ebiramu, 2020,295 (21): 7452-7469.DOI: 10.1074 / jbc.RA119.012094.
[2] Mitchell W, Ng E. A., Tamucci J. D., n’abalala. Enkola ya molekyu ey’okukola kwa Mitochondrial Therapeutic SS-31 (Elamipretide): Enkolagana y’olususu n’ebikosa ku masanyalaze ag’okungulu [J]. Biorxiv, 2019. DOI:10.1101/735001. Enkola y’okukuuma obutonde bw’ensi.
[3] Liu Y, Yang W, Sun X, n’abalala. SS31 Etereeza obuvune bw’omutima obuva ku Sepsis ng’eziyiza Oxidative Stress n’okuzimba[J]. Okuzimba, 2019, 42 (6): 2170-2180.DOI: 10.1007 / s10753-019-01081-3.
[4] Zhong L, Ren X, Ai Y, n’abalala. SS-31 Alongoosa Enkola y’Okutegeera mu Sepsis-Associated Encephalopathy nga Eziyiza Drp1-NLRP3 Inflammasome Activation[J]. Eddagala ly'obusimu, 2023,25 (2): 230-241. DOI:10.1007/s12017-022-08730-1.
[5] Broome SC, Woodhead JST, Merry T L. Ebirungo ebiziyiza obuwuka obuleeta obulwadde ebigendereddwamu mitochondria n’enkola y’ebinywa by’amagumba[J]. Ebiziyiza obuwuka obuleeta obulwadde, 2018,7 (8},ENNAMBA-EKIWANDI ={107).DOI:10.3390/antiox7080107.
[6] Rutkai I, Seman A, Chandra P, n’abalala. Emigaso gya SS-31 ku mbeba ezikaddiye cerebral microvasculature[J]. Enkola y’omubiri, 2023,38.DOI:10.1152/physiol.2023.38.S1.5734232.
EBINTU BYONNNA N’AMAWULIRE GW’EBINTU EBIweereddwa KU MUTINDO GUNO BIKOZESEBWA KU KUSASANYA AMAWULIRE N’EBIKOLWA BY’OKUSOMESA.
Ebintu ebiweereddwa ku mukutu guno bigendereddwamu kunoonyereza mu kisenge (in vitro research) byokka. Okunoonyereza mu vitro (Olulattini: *mu ndabirwamu*, ekitegeeza mu bikozesebwa mu ndabirwamu) kukolebwa ebweru w’omubiri gw’omuntu. Ebintu bino si bya ddagala, tebikkiriziddwa kitongole kya Amerika ekivunaanyizibwa ku by’emmere n’eddagala (FDA), era tebirina kukozesebwa kuziyiza, kujjanjaba oba kuwonya mbeera yonna ya bujjanjabi, bulwadde oba bulwadde. Kikugirwa nnyo mu mateeka okuyingiza ebintu bino mu mubiri gw’omuntu oba ebisolo mu ngeri yonna.