The Role of TPM3 in Protecting Cardiomyocyte from Hypoxia-Induced Injury via Cytoskeleton Stabilization.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Cell Hypoxia* ; Cytoskeleton*/metabolism ; Myocytes, Cardiac*/metabolism ; Myocytes, Cardiac*/pathology ; Oxidative Stress* ; Tropomyosin*/metabolism ; Tropomyosin*/genetics; Animals ; Rats ; Cell Line ; Cobalt/pharmacology ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics

Ischemic heart disease (IHD) remains a major global health concern, with ischemia-reperfusion injury exacerbating myocardial damage despite therapeutic interventions. In this study, we investigated the role of tropomyosin 3 (TPM3) in protecting cardiomyocytes against hypoxia-induced injury and oxidative stress. Using the AC16 and H9c2 cell lines, we established a chemical hypoxia model by treating cells with cobalt chloride (CoCl 2 ) to simulate low-oxygen conditions. We found that CoCl 2 treatment significantly upregulated the expression of hypoxia-inducible factor 1 alpha (HIF-1α) in cardiomyocytes, indicating the successful induction of hypoxia. Subsequent morphological and biochemical analyses revealed that hypoxia altered cardiomyocyte morphology disrupted the cytoskeleton, and caused cellular damage, accompanied by increased lactate dehydrogenase (LDH) release and malondialdehyde (MDA) levels, and decreased superoxide dismutase (SOD) activity, indicative of oxidative stress. Lentivirus-mediated TPM3 overexpression attenuated hypoxia-induced morphological changes, cellular damage, and oxidative stress imbalance, while TPM3 knockdown exacerbated these effects. Furthermore, treatment with the HDAC1 inhibitor MGCD0103 partially reversed the exacerbation of hypoxia-induced injury caused by TPM3 knockdown. Protein-protein interaction (PPI) network and functional enrichment analysis suggested that TPM3 may modulate cardiac muscle development, contraction, and adrenergic signaling pathways. In conclusion, our findings highlight the therapeutic potential of TPM3 modulation in mitigating hypoxia-associated cardiac injury, suggesting a promising avenue for the treatment of ischemic heart disease and other hypoxia-related cardiac pathologies.
Competing Interests: The authors declare no conflicts of interest.

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No. 23YFWA0003 the Key Research and Development Program of Gansu Province, China (International Scientific and Technological Cooperation Category); lzujbky-2023-07 the Fundamental Research Funds for the Central Universities, Lanzhou University; No. 2023-2-10 the Science and Technology Planning Project of Lanzhou, China; No.23JRRA0981 the Natural Science Foundation of Gansu Province; No.CY-2023- QY-B08 the Cuiying Science and Technology Innovation Project of Lanzhou University Second Hospital

Keywords: TPM3; cardiomyocyte injury; cytoskeleton; hypoxia; oxidative stress

3G0H8C9362 (Cobalt)
EVS87XF13W (cobaltous chloride)
0 (Hypoxia-Inducible Factor 1, alpha Subunit)
0 (Tropomyosin)
0 (TPM3 protein, human)

Date Created: 20240627 Date Completed: 20240627 Latest Revision: 20240717

20250114

PMC11203979

10.3390/ijms25126797

38928503