Function of mitochondrial cytochrome c oxidase is enhanced in human lens epithelial cells at high temperatures

Mol Med Rep. 2023 Jan;27(1):19. doi: 10.3892/mmr.2022.12906. Epub 2022 Dec 9.

Abstract

Enhancement of density via human lens epithelium (HLE) cell proliferation is the underlying cause of nuclear cataracts. Moreover, our previous epidemiological study demonstrated that the risk of nuclear cataract development is significantly higher under elevated environmental temperatures compared with under lower temperatures. The present study investigated the relationship between temperature and cell proliferation in terms of mitochondrial function, which is a nuclear cataract‑inducing risk factor, using two different HLE cell lines, SRA01/04 and immortalized human lens epithelial cells NY2 (iHLEC‑NY2). Cell proliferation was significantly enhanced under the high‑temperature condition (37.5˚C) in both cell lines. The cell growth levels of SRA01/04 and iHLEC‑NY2 cells cultured at 37.5˚C were 1.20‑ and 1.16‑fold those in the low‑temperature cultures (35.0˚C), respectively. Moreover, the levels of cytochrome c oxidase mRNA (mitochondrial genome, cytochrome c oxidase‑1‑3) and its activity in SRA01/04 and iHLEC‑NY2 cells cultured at 37.5˚C were higher compared with those in cells cultured at 35.0˚C. In addition, adenosine‑5'‑triphosphate (ATP) levels in SRA01/04 and iHLEC‑NY2 cells were also significantly higher at 37.5˚C compared with those at 35.0˚C. By contrast, no significant differences in Na+/K+‑ATPase or Ca2+‑ATPase activities were observed between HLE cells cultured at 35.0 and 37.5˚C. These results suggested that expression of the mitochondrial genome was enhanced in high‑temperature culture, resulting in a sufficient ATP content and cell proliferation for lens opacity. Therefore, elevated environmental temperatures may increase the risk of nuclear cataracts caused by HLE cell proliferation via mitochondrial activation.

Keywords: ATP; cell proliferation; cytochrome c oxidase; high‑temperature culture; human; lens epithelium cell.

MeSH terms

  • Adenosine Triphosphatases
  • Adenosine Triphosphate
  • Cataract* / etiology
  • Electron Transport Complex IV* / genetics
  • Epithelial Cells
  • Humans
  • Mitochondria

Substances

  • Electron Transport Complex IV
  • Adenosine Triphosphate
  • Adenosine Triphosphatases

Grants and funding

This study was supported by Otsuka Pharmaceutical Co., Ltd. (research grant program for ‘Relationships among environmental, body temperatures and cataracts’; grant no. 2020-R-091) and Alcon Japan Ltd. (grant no. 2021-R-087).