CaMKIIδ Antibody (Rabbit mAb) [E8P2]

카탈로그 번호 F2409

인쇄

생물학적 설명

특이성 CaMKIIδ Antibody (Rabbit mAb) [E8P2]은 내인성 수준의 전체 CaMKIIδ 단백질을 검출합니다.
배경 CaMKIIδ는 심장에서 우세한 Ca²⁺/칼모듈린 의존성 단백질 키나아제 II 이소형으로, 다중체 홀로효소로 조립되어 Ca²⁺, β-아드레날린 및 산화환원 신호의 중심 통합자 역할을 하며, 반복적인 Ca²⁺ 과도 상태를 흥분-수축 결합, 비대 성장 및 부정맥 유발을 촉진하는 이온 처리 단백질 및 전사 조절자의 지속적인 인산화로 변환합니다. 이 키나아제는 N-말단 촉매 도메인과 그 뒤를 잇는 CaM 결합 요소 및 Thr287 자가인산화 부위를 포함하는 자가억제 영역, 그리고 도데카머 및 더 큰 조립체로의 올리고머화를 촉진하는 C-말단 연관 도메인을 포함합니다. 이러한 구조는 서브유닛 간 자가인산화를 지원하며 Thr287 인산화, 메티오닌 산화 및 O-GlcNAc화를 통해 Ca²⁺ 의존적 활성에서 자율적 활성으로의 전환을 허용하여 CaMKIIδ가 초기 Ca²⁺ 펄스 후에도 활성 상태를 유지할 수 있도록 합니다. 심실 심근세포에서 CaMKIIδ는 L-형 Ca²⁺ 채널, 라이아노딘 수용체 2 및 포스포람반을 인산화하여 근세포막 Ca²⁺ 유입을 증가시키고, 근소포체 Ca²⁺ 누출을 강화하며, 근소포체 재충전을 가속화합니다. 이 네트워크의 만성적인 과활성화는 이완기 Ca²⁺ 과부하, 지연 후탈분극 및 심실 빈맥과 심방 세동의 기저가 되는 유발 활동으로 이어집니다. 동일한 키나아제는 또한 클래스 IIa 히스톤 탈아세틸화효소 HDAC4를 인산화하여 핵 배출 및 MEF2 의존적 유전자 프로그램의 탈억제를 유도하며, 이를 통해 Ca²⁺ 및 신경체액성 스트레스를 압력 과부하 및 신경호르몬 유발 심장 질환의 비대 유전자 발현, 섬유증 및 불리한 리모델링과 연결합니다. 횡단 대동맥 협착술을 받은 생쥐에서 CaMKIIδ의 유전적 결실은 심장 비대를 유지하지만 심부전으로의 전환을 현저히 약화시켜 심실 확장, 수축 기능 장애, 섬유증, 세포사멸 및 근소포체 Ca²⁺ 누출을 감소시키는 반면, CaMKIIδ의 형질전환 과발현은 활동 전위 연장, 자발적 후탈분극, 확장성 심근병증 및 급사 증가를 초래하여 이 이소형이 병리학적 심장 스트레스의 중요한 변환기임을 확인시켜 줍니다. 인간의 심부전 및 허혈성 심근병증 샘플은 CaMKIIδ 발현 및 자율적 활성 증가와 하류 Ca²⁺ 처리 표적의 인산화 증가를 보여주며, 구조적 심장 질환 모델에서의 약리학적 CaMKII 억제는 좌심실 기능을 개선하고 부정맥을 억제합니다.

사용 정보

응용 WB, IHC 희석
WB IHC
1:1000 - 1:2000 1:50 - 1:100
반응성 Mouse, Rat, Human
출처 Rabbit Monoclonal Antibody MW 56 kDa
보관 완충액 PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3
보관
(수령일로부터)
-20°C (avoid freeze-thaw cycles), 2 years
WB
Experimental Protocol:
 
Sample preparation
1. Tissue: Lyse the tissue sample by adding an appropriate volume of ice-cold RIPA/NP-40 Lysis Buffer (containing Protease Inhibitor Cocktail),and homogenize the tissue at a low temperature or lyse it by sonication on ice, then incubate on ice for 30 minutes.
2. Adherent cell: Aspirate the culture medium and wash the cells with ice-cold PBS twice. Lyse the cells by adding an appropriate volume of RIPA/NP-40 Lysis Buffer (containing Protease Inhibitor Cocktail) , sonicate to lyse the cells, and incubate on ice for 30 minutes.
3. Suspension cell: Transfer the culture medium to a pre-cooled centrifuge tube. Centrifuge and aspirate the supernatant. Wash the cells with ice-cold PBS twice. Lyse the cells by adding an appropriate volume of RIPA/NP-40 Lysis Buffer (containing Protease Inhibitor Cocktail) , sonicate to lyse the cells, and incubate on ice for 30 minutes.
4. Place the lysate into a pre-cooled microcentrifuge tube. Centrifuge at 4°C for 15 min. Collect the supernatant;
5. Remove a small volume of lysate to determine the protein concentration;
6. Combine the lysate with protein loading buffer. Boil 20 µL sample under 95-100°C for 5 min. Centrifuge for 5 min after cool down on ice.
 
Electrophoretic separation
1. According to the concentration of extracted protein, load appropriate amount of protein sample and marker onto SDS-PAGE gels for electrophoresis. Recommended separating gel (lower gel) concentration: 10%. Reference Table for Selecting SDS-PAGE Separation Gel Concentrations
2. Power up 80V for 30 minutes. Then the power supply is adjusted (110 V~150 V), the Marker is observed, and the electrophoresis can be stopped when the indicator band of the predyed protein Marker where the protein is located is properly separated. (Note that the current should not be too large when electrophoresis, too large current (more than 150 mA) will cause the temperature to rise, affecting the result of running glue. If high currents cannot be avoided, an ice bath can be used to cool the bath.)
 
Transfer membrane
1. Take out the converter, soak the clip and consumables in the pre-cooled converter;
2. Activate PVDF membrane with methanol for 1 min and rinse with transfer buffer;
3. Install it in the order of "black edge of clip - sponge - filter paper - filter paper - glue -PVDF membrane - filter paper - filter paper - sponge - white edge of clip";
4. The protein was electrotransferred to PVDF membrane. ( 0.45 µm PVDF membrane is recommended ) Reference Table for Selecting PVDF Membrane Pore Size Specifications
Recommended conditions for wet transfer: 200 mA, 120 min.
( Note that the transfer conditions can be adjusted according to the protein size. For high-molecular-weight proteins, a higher current and longer transfer time are recommended. However, ensure that the transfer tank remains at a low temperature to prevent gel melting.)
 
Block
1. After electrotransfer, wash the film with TBST at room temperature for 5 minutes;
2. Incubate the film in the blocking solution for 1 hour at room temperature;
3. Wash the film with TBST for 3 times, 5 minutes each time.
 
Antibody incubation
1. Use primary antibody dilution buffer to prepare the primary antibody working liquid (recommended dilution ratio for primary antibody 1:1000), gently shake and incubate with the film at 4°C overnight;
2. Wash the film with TBST 3 times, 5 minutes each time;
3. Add the secondary antibody to the blocking solution and incubate with the film gently at room temperature for 1 hour;
4. After incubation, wash the film with TBST 3 times for 5 minutes each time.
 
Antibody staining
1. Add the prepared ECL luminescent substrate (or select other color developing substrate according to the second antibody) and mix evenly;
2. Incubate with the film for 1 minute, remove excess substrate (keep the film moist), wrap with plastic film, and expose in the imaging system.
IHC
Experimental Protocol:
 
Deparaffinization/Rehydration
1. Deparaffinize/hydrate sections:
2. Incubate sections in three washes of xylene for 5 min each.
3. Incubate sections in two washes of 100% ethanol for 10 min each.
4. Incubate sections in two washes of 95% ethanol for 10 min each.
5. Wash sections two times in dH2O for 5 min each.
6.Antigen retrieval: For Citrate: Heat slides in a microwave submersed in 1X citrate unmasking solution until boiling is initiated; continue with 10 min at a sub-boiling temperature (95°-98°C). Cool slides on bench top for 30 min.
 
Staining
1. Wash sections in dH2O three times for 5 min each.
2. Incubate sections in 3% hydrogen peroxide for 10 min.
3. Wash sections in dH2O two times for 5 min each.
4. Wash sections in wash buffer for 5 min.
5. Block each section with 100–400 µl of blocking solution for 1 hr at room temperature.
6. Remove blocking solution and add 100–400 µl primary antibody diluent in to each section. Incubate overnight at 4°C.
7. Remove antibody solution and wash sections with wash buffer three times for 5 min each.
8. Cover section with 1–3 drops HRPas needed. Incubate in a humidified chamber for 30 min at room temperature.
9. Wash sections three times with wash buffer for 5 min each.
10. Add DAB Chromogen Concentrate to DAB Diluent and mix well before use.
11. Apply 100–400 µl DAB to each section and monitor closely. 1–10 min generally provides an acceptable staining intensity.
12. Immerse slides in dH2O.
13. If desired, counterstain sections with hematoxylin.
14. Wash sections in dH2O two times for 5 min each.
15. Dehydrate sections: Incubate sections in 95% ethanol two times for 10 sec each; Repeat in 100% ethanol, incubating sections two times for 10 sec each; Repeat in xylene, incubating sections two times for 10 sec each.
16. Mount sections with coverslips and mounting medium.
 

참조

  • https://pubmed.ncbi.nlm.nih.gov/19179290/
  • https://journals.physiology.org/doi/full/10.1152/physrev.00018.2010

적용 데이터

WB

Selleck 검증

  • F2409-wb
    Lane 1: Hela, Lane 2: SW480, Lane 3: A431, Lane 4: Mouse heart